Glycine → ([1-(4-Acetylamino-phenoxy)-4-hydroxy-isoquinoline-3-carbonyl]-amino)-acetic acid
Reaction equation
C(O[C:6]([C:8]1[N:9]=[C:10]([O:22][C:23]2[CH:28]=[CH:27][C:26]([NH:29][C:30](=[O:32])[CH3:31])=[CH:25][CH:24]=2)[C:11]2[C:16]([C:17]=1[O:18]C(=O)C)=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])CCC.[NH2:33][CH2:34][C:35]([OH:37])=[O:36].C[O-].[Na+].CO>>[C:30]([NH:29][C:26]1[CH:25]=[CH:24][C:23]([O:22][C:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:17]([OH:18])=[C:8]([C:6]([NH:33][CH2:34][C:35]([OH:37])=[O:36])=[O:7])[N:9]=2)=[CH:28][CH:27]=1)(=[O:32])[CH3:31]Participants
5
Procedure
A mixture of 4-Acetoxy-1-(4-acetylamino-phenoxy)-isoquinoline-3-carboxylic acid butyl ester (150 mg, 0.34 mmol), glycine (290 mg, 3.4 mmol), and 7.8 ml of a 0.5 N solution of sodium methoxide in methanol (3.9 mmol) was refluxed over the weekend with stirring. Then the solvent was evaporated in vacuo and the residue dissolved in 25 ml of water. The pH of the solution was subsequently adjusted to about 2 and the resulting slurry was extracted with ethyl acetate (3×30 ml). The combined extracts were dried over MgSO4 and evaporated in vacuo. Recrystallization of the residue from methanol/CH2Cl2 gave 86 mg of the title compound; MS-(+)-ion: M+1=396.15.
Workup
- temperaturewas refluxed over the weekend
- customThen the solvent was evaporated in vacuo
- dissolutionthe residue dissolved in 25 ml of water
- extractionthe resulting slurry was extracted with ethyl acetate (3×30 ml)
- dry with materialThe combined extracts were dried over MgSO4
- customevaporated in vacuo
- customRecrystallization of the residue from methanol/CH2Cl2
Sources & evidence
- ORD record
- ord-693af45f241d47bc9c1176f366d8056d
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08916585B2
Reaction notes
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