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

HRID 1481179Notes

Reaction equation

C[O:2][C:3]([C:5]1[N:6]=[C:7]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[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.OC(C(F)(F)F)=O.[NH2:36][CH2:37][C:38]([CH3:43])([CH3:42])[C:39]([OH:41])=[O:40].C[O-].[Na+]>CCO>[OH:15][C:14]1[C:13]2[C:8](=[CH:9][C:10]([O:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:11][CH:12]=2)[C:7]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[N:6][C:5]=1[C:3]([NH:36][CH2:37][C:38]([CH3:43])([CH3:42])[C:39]([OH:41])=[O:40])=[O:2]

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 4-hydroxy-7-phenoxy-1-phenyl-isoquinoline-3-carboxylic acid methyl ester (50 mg, 0.13 mmol), 3-amino-2,2-dimethyl-propionic acid TFA salt (125 mg, 0.54 mmol) and NaOMe (58 mg, 1.08 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 44 mg of the title compound as a yellow solid. MS: (+) m/z 457.26 (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-09acac745a254f0c89ce99f02aacc42e
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409892B2

Reaction notes

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