Acetic Acid → Methyl 1-(4-chloro-7H-pyrrolo[2,3-D]pyrimidin-7-YL)cyclopropanecarboxylate
Reaction equation
Cl[C:2]1[C:7]([CH2:8][CH:9]=O)=[C:6]([Cl:11])[N:5]=[CH:4][N:3]=1.Cl.[CH3:13][O:14][C:15]([C:17]1([NH2:20])[CH2:19][CH2:18]1)=[O:16].C(N(CC)CC)C.C(O)(=O)C>C(O)C.C(Cl)Cl>[CH3:13][O:14][C:15]([C:17]1([N:20]2[C:2]3[N:3]=[CH:4][N:5]=[C:6]([Cl:11])[C:7]=3[CH:8]=[CH:9]2)[CH2:19][CH2:18]1)=[O:16]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 100 °C
Procedure
To a stirred solution of (4,6-dichloro-pyrimidin-5-yl)acetaldehyde (Preparation 208, 2 g, 10.5 mmol) and 1-Amino-cyclopropane-carboxylicacidmethylester hydrochloride (1.33 g, 11.6 mmol) in ethanol (30 mL) was added triethylamine (4.4 mL, 31.6 mmol) and the mixture heated in a sealed tube at 100° C. for 10 hours. Acetic acid (1.21 mL, 21.1 mmol) was then added and the mixture heated at 100° C. for additional 16 hours. The reaction mixture was cooled to room temperature and diluted with DCM (200 mL). The organic layer was washed with water (2×50 mL), brine (50 mL), dried (Na2SO4) and evaporated in vacuo. The crude material was purified by column chromatography on silica gel (gradient of hexane:EtOAc 100:0 to 90:10) to afford the title compound as a solid in 35% yield, 900 mg.
Workup
- temperaturethe mixture heated at 100° C. for additional 16 hours
- temperatureThe reaction mixture was cooled to room temperature
- washThe organic layer was washed with water (2×50 mL), brine (50 mL)
- dry with materialdried (Na2SO4)
- customevaporated in vacuo
- customThe crude material was purified by column chromatography on silica gel (gradient of hexane:EtOAc 100:0 to 90:10)
Sources & evidence
- ORD record
- ord-cecf0446fec84d23845977796d2ede3f
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08846698B2
Reaction notes
Loading…