Hydrochloric Acid → 3-(R)-[(1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]-butyric acid

HRID 1481063Notes

Reaction equation

CO[C:3]([C:5]1[N:6]=[C:7]([C:23]#[N:24])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]=2)=[O:4].[NH2:25][C@H:26]([CH3:31])[CH2:27][C:28]([OH:30])=[O:29].C[O-].[Na+].Cl>CN(C)C=O.O.ClCCl>[C:23]([C:7]1[C:8]2[C:13](=[CH:12][CH:11]=[C:10]([O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:9]=2)[C:14]([OH:15])=[C:5]([C:3]([NH:25][C@H:26]([CH3:31])[CH2:27][C:28]([OH:30])=[O:29])=[O:4])[N:6]=1)#[N:24]

Participants

Conditions

Temperature: 140 °C

Procedure

1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (75 mg, 0.234 mmol) and 3-(R)-amino-butyric acid (103 mg, 1.0 mmol) were placed in a CEM 10 mL Microwave vessel and dissolved in anhydrous N,N-dimethylformamide (2 mL.) Sodium methoxide (54 mg, 1.0 mmol) was added to solution and the vessel was sealed. The reaction was heated to 140° C. in a CEM microwave apparatus for four hours. Upon completion, the reaction mixture was diluted with water and treated with 1N hydrochloric acid. The precipitate was dissolved in dichloromethane and dried over anhydrous sodium sulfate. The crude product was purified by MPLC (methylene chloride-ethyl acetate) to provide the title compound as a light-yellow solid in 75% yield. MS ESI(−) m/e: 390.091 (M−1).

Workup

additionwas added to solution
customthe vessel was sealed
dry with materialdried over anhydrous sodium sulfate
customThe crude product was purified by MPLC (methylene chloride-ethyl acetate)

Sources & evidence

ORD record: ord-49c2b9c247c14211babe2752638627b3
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409892B2

Reaction notes

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