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

HRID 1481183Notes

Reaction equation

CO[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]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]=2)=[O:4].OC(C(F)(F)F)=O.[NH2:30][CH2:31][C:32]([CH3:37])([CH3:36])[C:33]([OH:35])=[O:34].C[O-].[Na+]>CCO>[CH2:16]([C:10]1[CH:9]=[C:8]2[C:13]([C:14]([OH:15])=[C:5]([C:3]([NH:30][CH2:31][C:32]([CH3:37])([CH3:36])[C:33]([OH:35])=[O:34])=[O:4])[N:6]=[CH:7]2)=[CH:12][CH:11]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 7-benzyl-4-hydroxy-isoquinoline-3-carboxylic acid methyl ester (19 mg, 0.065 mmol), 3-amino-2,2-dimethyl-propionic acid TFA salt (60 mg, 0.26 mmol) and NaOMe (28 mg, 0.52 mmol) in EtOH (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 (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 (0-30% EtOAc/hexanes+2% AcOH) to give 9.5 mg of the title compound. MS: (+) m/z 379.17 (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 (0-30% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record: ord-1f2e6334adfa487b979c3bda1d82fc22
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409892B2

Reaction notes

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