Category: 1001180-21-7

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1001180-21-7,(R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

A flask was equipped with a thermocouple, mechanic stirrer, a nitrogen inlet and drying tube. To the flask was added (R)-tert-buty 4-(5-methyl-7-oxo-6,7-dihydro-5H- cyclopenta[i ]pyrimidin-4-yl)piperazine-l -carboxylate (46.0 g, 139 mmol) followed by dichloromethane (1.10 L) and RuCl(TsDACH) catalyst (1.50 g, 2.80 mmol) with nitrogen degassing (gas dispersion tube) and agitation at room temperature. To the mixture was added triethylamine (23.0 mL, 167 mmol) with degassing. Formic acid (7.40 mL, 195 mmol) was slowly added to the mixture at a rate of about 1 mL/min. Good agitation with stirring was maintained until complete consumption of starting material (about 8-12 hr) as determined by HPLC analysis. The reaction was quenched with saturated sodium bicarbonate (2.00 vol., 100 mL), the layers were separated and the aqueous layer was discarded. The organic layer was washed with saturated sodium bicarbonate, saturated ammonium chloride and brine (2.00 vol., 100 mL each). The organics were dried over sodium sulfate, filtered and solvent exchanged into methanol. The methanolic solution (5.00 vol.) of crude product was charged with 50 wt % SiliaBond Thiol (Silicycle, Inc.) and 20 wt% Charcoal. The mixture was heated to about 50 C and maintained at that temperature with good stirring overnight. The mixture was cooled to room temperature, filtered over a pad of Celite and then polish filtered through a 0.45 micron filter. The mixture was distilled to a minimum working volume and concentrated under reduced pressure to afford the product (44.0 g, 95 % yield), as a 96:4 mixture of trans/cis diastereomers) as solid. Trace amount of Ru metal was measured by ICP-EOS and found that the product contained less than about 20 ppm Ru. The product was purified by preparative HPLC under the following conditionsor crystallization from ethyl acetate/heptane to yield 98.4 % pure product, 97.7 % de with about 100% ee., 1001180-21-7

The synthetic route of 1001180-21-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ARRAY BIOPHARMA INC.; GENENTECH, INC.; LANE, Jonathan W.; REMARCHUK, Travis; SHAKYA, Sagar; SPENCER, Keith L.; STENGEL, Peter J.; WO2013/173736; (2013); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

1001180-21-7, (R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 40; 2-(4-chlorophenyl)-l-(‘4-((5R)-7-hydroxy-5,7-diniethyl-6,7-dihvdro-5H-cvclopenta[dlpyrimidin-4- vDpiperazin- 1 -ylV S-fisopropylamino’propan- 1 -one; Step 1 :; A solution of (R)-tert-butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H- cyclopenta[d]pyrimidin-4-yl)piperazine-l-carboxylate (40 nig, 0.120 mmol) in THF (4 niL) was added to a 1.5M solution of methyllithium in diethyl ether (0.088 mL, 0.132 mmol) at -780C. The resulting mixture was stirred at -78C for 1 hour and quenched by saturated aqueous NH4Cl. The aqueous layer was extracted with EtOAc (2 X). The organic layer was dried (MgSO^ and concentrated. The residue was purified by a silica catridge (5.0 g) eluted by EtOAc to give tert-butyl 4-((5R)-7-hydroxy-5,7-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine- 1-carboxylate as an off-white solid (29 mg, 69%). LCMS (APCI+) [M-Boc+H]+ 349.1; Rt: 2.49 min.

1001180-21-7, The synthetic route of 1001180-21-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ARRAY BIOPHARMA INC.; GENENTECH, INC.; MITCHELL, Ian, S.; BLAKE, James, F.; XU, Rui; KALLAN, Nicholas, C.; XIAO, Dengming; SPENCER, Keith, Lee; BENCSIK, Josef, R.; LIANG, Jun; SAFINA, Brian; ZHANG, Birong; CHABOT, Christine; DO, Steven; WO2008/6040; (2008); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1001180-21-7,(R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

A flask was equipped with a thermocouple, mechanic stirrer, a nitrogen inlet and drying tube. To the flask was added (R)-tert-buty 4-(5-methyl-7-oxo-6,7-dihydro-5H- cyclopenta[i ]pyrimidin-4-yl)piperazine-l -carboxylate (46.0 g, 139 mmol) followed by dichloromethane (1.10 L) and RuCl(TsDACH) catalyst (1.50 g, 2.80 mmol) with nitrogen degassing (gas dispersion tube) and agitation at room temperature. To the mixture was added triethylamine (23.0 mL, 167 mmol) with degassing. Formic acid (7.40 mL, 195 mmol) was slowly added to the mixture at a rate of about 1 mL/min. Good agitation with stirring was maintained until complete consumption of starting material (about 8-12 hr) as determined by HPLC analysis. The reaction was quenched with saturated sodium bicarbonate (2.00 vol., 100 mL), the layers were separated and the aqueous layer was discarded. The organic layer was washed with saturated sodium bicarbonate, saturated ammonium chloride and brine (2.00 vol., 100 mL each). The organics were dried over sodium sulfate, filtered and solvent exchanged into methanol. The methanolic solution (5.00 vol.) of crude product was charged with 50 wt % SiliaBond Thiol (Silicycle, Inc.) and 20 wt% Charcoal. The mixture was heated to about 50 C and maintained at that temperature with good stirring overnight. The mixture was cooled to room temperature, filtered over a pad of Celite and then polish filtered through a 0.45 micron filter. The mixture was distilled to a minimum working volume and concentrated under reduced pressure to afford the product (44.0 g, 95 % yield), as a 96:4 mixture of trans/cis diastereomers) as solid. Trace amount of Ru metal was measured by ICP-EOS and found that the product contained less than about 20 ppm Ru. The product was purified by preparative HPLC under the following conditionsor crystallization from ethyl acetate/heptane to yield 98.4 % pure product, 97.7 % de with about 100% ee., 1001180-21-7

The synthetic route of 1001180-21-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ARRAY BIOPHARMA INC.; GENENTECH, INC.; LANE, Jonathan W.; REMARCHUK, Travis; SHAKYA, Sagar; SPENCER, Keith L.; STENGEL, Peter J.; WO2013/173736; (2013); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1001180-21-7,(R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

A flask was equipped with a thermocouple, mechanic stirrer, a nitrogen inlet and drying tube. To the flask was added (R)-tert-buty 4-(5-methyl-7-oxo-6,7-dihydro-5H- cyclopenta[i ]pyrimidin-4-yl)piperazine-l -carboxylate (46.0 g, 139 mmol) followed by dichloromethane (1.10 L) and RuCl(TsDACH) catalyst (1.50 g, 2.80 mmol) with nitrogen degassing (gas dispersion tube) and agitation at room temperature. To the mixture was added triethylamine (23.0 mL, 167 mmol) with degassing. Formic acid (7.40 mL, 195 mmol) was slowly added to the mixture at a rate of about 1 mL/min. Good agitation with stirring was maintained until complete consumption of starting material (about 8-12 hr) as determined by HPLC analysis. The reaction was quenched with saturated sodium bicarbonate (2.00 vol., 100 mL), the layers were separated and the aqueous layer was discarded. The organic layer was washed with saturated sodium bicarbonate, saturated ammonium chloride and brine (2.00 vol., 100 mL each). The organics were dried over sodium sulfate, filtered and solvent exchanged into methanol. The methanolic solution (5.00 vol.) of crude product was charged with 50 wt % SiliaBond Thiol (Silicycle, Inc.) and 20 wt% Charcoal. The mixture was heated to about 50 C and maintained at that temperature with good stirring overnight. The mixture was cooled to room temperature, filtered over a pad of Celite and then polish filtered through a 0.45 micron filter. The mixture was distilled to a minimum working volume and concentrated under reduced pressure to afford the product (44.0 g, 95 % yield), as a 96:4 mixture of trans/cis diastereomers) as solid. Trace amount of Ru metal was measured by ICP-EOS and found that the product contained less than about 20 ppm Ru. The product was purified by preparative HPLC under the following conditionsor crystallization from ethyl acetate/heptane to yield 98.4 % pure product, 97.7 % de with about 100% ee., 1001180-21-7

The synthetic route of 1001180-21-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; ARRAY BIOPHARMA INC.; GENENTECH, INC.; LANE, Jonathan W.; REMARCHUK, Travis; SHAKYA, Sagar; SPENCER, Keith L.; STENGEL, Peter J.; WO2013/173736; (2013); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

1001180-21-7, (R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step 9: Triethylamine (4.33 ml, 31.1 mmol; degassed with nitrogen 30 minutes prior to use) and formic acid (1.36 ml, 36.1 mmol; degassed with nitrogen 30 minutes prior to use) were added to a solution of (R)-tert-butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H- cyclopenta[d]pyrimidin-4-yl)piperazine-l-carboxylate (9.75 g, 29.3 mmol) in DCM (210 mL; degassed with nitrogen 30 minutes prior to use). The mixture was stirred for 5 minutes, then a Ru catalyst (0.0933 g, 0.147 mmol) was added. The reaction was stirred under positive nitrogen pressure overnight (18 hours). The reaction mixture was concentrated to dryness and dried on high vacuum. The impure material was flashed on Biotage 65M loaded 1 : 1 DCM:ethyl acetate 500 mL flushed, then 1 :4 DCM:ethyl acetate until product (2nd spot), then gradient to neat ethyl acetate, then 25:1 DCM:MeOH eluted rest of product. The fractions were combined and concentrated on a rotary evaporator. The residue was concentrated again from DCM/hexanes to give a mixture of tert-butyl 4-((5R,7R)-7-hydroxy- 5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine- 1 -carboxylate (major) and tert-butyl 4-((5R,7S)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4- yl)piperazine-l -carboxylate (minor) (9.35 g, 95.3% yield) as a beige foam. LC/MS (APCI+) m/z 335 [M+H]+. 1H NMR (CDC13) shows 88% de by integration of carbinol methine., 1001180-21-7

1001180-21-7 (R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate 59580350, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; GENENTECH, INC.; HOEFLICH, Klaus; MERCHANT, Mark; WO2012/135750; (2012); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

1001180-21-7, (R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step 9: Triethylamine (4.33 ml, 31.1 mmol; degassed with nitrogen 30 minutes prior to use) and formic acid (1.36 ml, 36.1 mmol; degassed with nitrogen 30 minutes prior to use) were added to a solution of (R)-tert-butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H- cyclopenta[d]pyrimidin-4-yl)piperazine-l-carboxylate (9.75 g, 29.3 mmol) in DCM (210 mL; degassed with nitrogen 30 minutes prior to use). The mixture was stirred for 5 minutes, then a Ru catalyst (0.0933 g, 0.147 mmol) was added. The reaction was stirred under positive nitrogen pressure overnight (18 hours). The reaction mixture was concentrated to dryness and dried on high vacuum. The impure material was flashed on Biotage 65M loaded 1 : 1 DCM:ethyl acetate 500 mL flushed, then 1 :4 DCM:ethyl acetate until product (2nd spot), then gradient to neat ethyl acetate, then 25:1 DCM:MeOH eluted rest of product. The fractions were combined and concentrated on a rotary evaporator. The residue was concentrated again from DCM/hexanes to give a mixture of tert-butyl 4-((5R,7R)-7-hydroxy- 5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine- 1 -carboxylate (major) and tert-butyl 4-((5R,7S)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4- yl)piperazine-l -carboxylate (minor) (9.35 g, 95.3% yield) as a beige foam. LC/MS (APCI+) m/z 335 [M+H]+. 1H NMR (CDC13) shows 88% de by integration of carbinol methine., 1001180-21-7

1001180-21-7 (R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate 59580350, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; GENENTECH, INC.; HOEFLICH, Klaus; MERCHANT, Mark; WO2012/135750; (2012); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

1001180-21-7, (R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step 4: (Reaction run in a 20-mL plastic bottle): To a solution of (R)-tert-butyl 4-(5- methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-l-carboxylate (0.250 g, 0.752 mmol) in 5 mL DCM was added DAST (0.795 mL, 6.02 mmol). The reaction mixture was capped and stirred at room temperature for 45 hours, after which it poured into ice saturated NaHCO3. The mixture was extracted with 2 x 40 mL DCM, and the combined extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The crude was purified on silica gel (Biotage 40S) eluting with 6:1 to 3:1 hexanes:EtOAc to give (R)-tert-butyl 4-(7,7-difluoro-5-methyl-6,7-dihydro- SH-cyclopenta^pyrimidin^-ytypiperazine-l-carboxylate (0.092 g, 34.5% yield) as a yellow oil. MS (APCI+) m/z 355 [M+H]+.

1001180-21-7, 1001180-21-7 (R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate 59580350, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ARRAY BIOPHARMA INC.; GENENTECH, INC.; MITCHELL, Ian S.; BLAKE, James F.; XU, Rui; KALLAN, Nicholas C.; XIAO, Dengming; SPENCER, Keith Lee; BENCSIK, Josef R.; LIANG, Jun; SAFINA, Brian; LI, Jun; CHABOT, Christine; WO2008/6032; (2008); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

1001180-21-7, (R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step 9: Triethylamine (4.33 mL, 31.1 mmol) (degassed with nitrogen 30 minutes prior to use) and formic acid (1.36 mL, 36.1 mmol) (degassed with nitrogen 30 minutes prior to use) were added to a solution of (R)-tert-butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H- cyclopenta[d]pyrimidin-4-yl)piperazine-l -carboxylate (9.75 g, 29.3 mmol) in DCM (210 mL; degassed with nitrogen 30 minutes prior to use). The reaction mixture was stirred for 5 minutes, and then a Ru catalyst (0.0933 g, 0.147 mmol) was added. The reaction was stirred under positive nitrogen pressure overnight (18 hours). The reaction mixture was concentrated to dryness and dried on a high vacuum. 1H NMR of the crude looked like 85% diastereoselectivity. The crude was flashed on Biotage 65M (loaded 1:1 DCM:ethyl acetate 500 mL flushed, then 1:4 DCM:ethyl acetate until product (2nd spot), then gradient to neat ethyl acetate, then 25:1 DCM:MeOH eluted rest of product. The fractions were combined and concentrated on a rotary evaporator. The residue was concentrated again from DCM/hexanes to give a mixture of tert-butyl 4-((5R,7R)-7-hydroxy-5- methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-l -carboxylate (major) and tert- butyl 4-((5R,7S)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-l- carboxylate (minor) (9.35 g, 95.3% yield) as a beige foam. LC/MS (APCI+) m/z 335 [M+H]+. 1U NMR (CDC13) shows 88% diastereoselectivity by integration of carbinol methine., 1001180-21-7

1001180-21-7 (R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate 59580350, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ARRAY BIOPHARMA INC.; GENENTECH, INC.; MITCHELL, Ian S.; BLAKE, James F.; XU, Rui; KALLAN, Nicholas C.; XIAO, Dengming; SPENCER, Keith Lee; BENCSIK, Josef R.; LIANG, Jun; SAFINA, Brian; LI, Jun; CHABOT, Christine; WO2008/6032; (2008); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

1001180-21-7, (R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step 11: Triethylamine (4.33 mL, 31.1 mmol; degassed with nitrogen 30 minutes prior to use) and formic acid (1.36 mL, 36.1 mmol; degassed with nitrogen 30 minutes prior to use) were added to a solution of (R)-tert-butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H- cyclopenta[d]pyrimidin-4-yl)piperazine-l-carboxylate (9.75 g, 29.3 mmol) in DCM (210 mL; degassed with nitrogen 30 minutes prior to use). The mixture was stirred for 5 minutes, and then a Ru catalyst (0.0933 g, 0.147 mmol) was added. The reaction was stirred under positive nitrogen pressure overnight (18 hours). The reaction mixture was concentrated to dryness and dried on high vacuum. The impure material was flashed on Biotage 65M loaded 1:1 DCM:ethyl acetate 500 mL flushed, then 1 :4 DCM:ethyl acetate until product (2nd spot), then gradient to neat ethyl acetate, then 25:1 DCM:MeOH eluted rest of product. The fractions were combined and concentrated on a rotary evaporator. The residue was concentrated again from DCM/hexanes to give a mixture of tert-butyl 4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H- cyclopenta[d]pyrimidin-4-yl)piperazine-l-carboxylate (major) and tert-butyl 4-((5R,7S)-7- hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-l-carboxylate (minor) (9.35 g, 95.3% yield) as a foam. LC/MS (APCI+) m/z 335 [M+H]+. 1H NMR (CDCl3) showed 88% diastereoselectivity by integration of carbinol methine., 1001180-21-7

As the paragraph descriping shows that 1001180-21-7 is playing an increasingly important role.

Reference：
Patent; ARRAY BIOPHARMA INC.; GENENTECH, INC.; WO2009/89453; (2009); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1001180-21-7,(R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Example 13aTert-butyl 4- [(5R,7R)-7-hydroxy-5-methyl-6,7-dihydrocyclopentaldl pyrimidin-4- yllpiperazine-1-carboxylate mM Potassium dihydrogen phosphate pH 7.2), 78 g 2-Propanol and 50 mg NAD (75iimol) was formed under vigorous stirring. The reduction started by the addition of 500 mg KRED-X1.1- P1 FO 1. The reaction mixture is sparged with nitrogen and heated to 40C for 22 hours. After reaction completion 174 g isopropylacetate are added, agitated, phases were split and the5 aqueous phase removed. The aqueous phase was extracted again with 174 g isopropylacetate. The aqueous phase was removed and the organic phases were combined and concentrated at 35C in vacuo to a final volume of 115 mL. At the same temperature 212 g Heptane are added within 1 hour, the suspension is aged for 1 hour and cooled to 10C within 6 hours. The suspension is filtered and washed with 68g heptane. After drying of the filter cake for 4 hours at10 50C and 41.1 g (82% yield, purity 100% area) white crystals are obtained.

1001180-21-7, 1001180-21-7 (R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate 59580350, apiperazines compound, is more and more widely used in various fields.

Reference£º
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; IDING, Hans; REENTS, Reinhard; SCALONE, Michelangelo; GOSSELIN, Francis; WO2015/73739; (2015); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics