Sodium Methoxide → 3-[(1-Cyano-4-hydroxy-7-phenyl-isoquinoline-3-carbonyl)-amino]-2,2-dimethyl-propionic acid

HRID 1481166Notes

Reaction equation

CO[C:3]([C:5]1[N:6]=[C:7]([C:22]#[N:23])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH:9]=2)=[O:4].OC(C(F)(F)F)=O.[NH2:31][CH2:32][C:33]([CH3:38])([CH3:37])[C:34]([OH:36])=[O:35].C[O-].[Na+]>CCO>[C:22]([C:7]1[C:8]2[C:13](=[CH:12][CH:11]=[C:10]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:9]=2)[C:14]([OH:15])=[C:5]([C:3]([NH:31][CH2:32][C:33]([CH3:38])([CH3:37])[C:34]([OH:36])=[O:35])=[O:4])[N:6]=1)#[N:23]

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 1-cyano-4-hydroxy-7-phenyl-isoquinoline-3-carboxylic acid methyl ester (47 mg, 0.15 mmol), 3-amino-2,2-dimethyl-propionic acid TFA salt (143 mg, 0.62 mmol) and NaOMe (67 mg, 1.24 mmol) in EtOH (3 mL) was heated at 150° C. in a microwave reactor for 2 h. The solvent was evaporated, and the residue was partitioned between water (30 mL) and EtOAc (30 mL). 1 M HCl was added with vigorous stirring until pH was ˜2. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by column chromatography (0-25% EtOAc/hexanes+2% AcOH) to give 36 mg of the title compound as a light brown solid. MS: (−) m/z 388.13 (M−1).

Workup

customThe solvent was evaporated
customthe residue was partitioned between water (30 mL) and EtOAc (30 mL)
addition1 M HCl was added
dry with materialThe organic layer was dried over MgSO4
concentrationconcentrated
customThe crude product was purified by column chromatography (0-25% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record: ord-691a130d4a324cdca5bd02b704be2923
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409892B2

Reaction notes

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