Methanol → 2-(S)-{[7-(4-Fluoro-phenoxy)-4-hydroxy-1-methyl-isoquinoline-3-carbonyl]-amino}-propionic acid
Reaction equation
C(O[C:6]([C:8]1[N:9]=[C:10]([CH3:27])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[CH:12]=2)=[O:7])CCC.[NH2:28][C@H:29]([C:31]([OH:33])=[O:32])[CH3:30].CO[Na].CO>>[F:26][C:23]1[CH:22]=[CH:21][C:20]([O:19][C:13]2[CH:12]=[C:11]3[C:16]([C:17]([OH:18])=[C:8]([C:6]([NH:28][C@@H:29]([CH3:30])[C:31]([OH:33])=[O:32])=[O:7])[N:9]=[C:10]3[CH3:27])=[CH:15][CH:14]=2)=[CH:25][CH:24]=1Participants
5
Reactant 4
Product 1
Conditions
- Temperature
- 140 °C
Procedure
A mixture of 7-(4-Fluoro-phenoxy)-4-hydroxy-1-methyl-isoquinoline-3-carboxylic acid butyl ester (92 mg, 0.25 mmol), (S)-alanine (225 mg, 2.5 mmol) and a 0.5N solution of MeONa in MeOH (5 ml, 2.5 mmol) was heated in a microwave oven with stirring for 20 min at 140° C. before the mixture was concentrated in vacuo. To the residue was added water (10 ml) and the mixture was washed with EtOAc (2×25 ml). The so purified aq. solution was acidified by the addition of 6N HCl and extracted with EtOAc (1×25 ml). The organic phase was dried over MgSO4 and concentrated in vacuo to give the title compound as a tan solid (69 mg); MS-(+)-ion M+1=385.1.
Workup
- concentrationwas concentrated in vacuo
- additionTo the residue was added water (10 ml)
- washthe mixture was washed with EtOAc (2×25 ml)
- customThe so purified aq. solution
- additionwas acidified by the addition of 6N HCl
- extractionextracted with EtOAc (1×25 ml)
- dry with materialThe organic phase was dried over MgSO4
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-37da61882c084d1182019daef0d13188
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09339527B2
Reaction notes
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