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

HRID 1481154Notes

Reaction equation

C[O:2][C:3]([C:5]1[N:6]=[CH:7][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.OC(C(F)(F)F)=O.[NH2:29][CH2:30][C:31]([CH3:36])([CH3:35])[C:32]([OH:34])=[O:33].C[O-].[Na+]>CCO>[OH:15][C:14]1[C:13]2[C:8](=[CH:9][C:10]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:11][CH:12]=2)[CH:7]=[N:6][C:5]=1[C:3]([NH:29][CH2:30][C:31]([CH3:36])([CH3:35])[C:32]([OH:34])=[O:33])=[O:2]

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 4-hydroxy-7-phenyl-isoquinoline-3-carboxylic acid methyl ester (60 mg, 0.22 mmol), 3-amino-2,2-dimethyl-propionic acid TFA salt (200 mg, 0.86 mmol) and NaOMe (93 mg, 1.72 mmol) in EtOH (2.2 mL) was heated at 150° C. in a microwave reactor for 6 h. The solvent was evaporated, and the residue was partitioned between water and EtOAc. 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 (0-30% EtOAc/hexanes+2% AcOH) to give 38 mg of the title compound. MS: (+) m/z 365.11 (M+1).

Workup

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

Sources & evidence

ORD record: ord-cb109ea2162645b3aef696f0190bebb7
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409892B2

Reaction notes

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