Dimethylformamide → tert-Butyl 2-(5-(2-(3-fluoro-4-(trifluoromethyl)phenyl)acetamido)-6-methyl-1-oxoisoquinolin-2(1H)-yl)ethyl(methyl)carbamate

HRID 418528Notes

Reaction equation

HRID 418528 reaction equation
[NH2:1][C:2]1[C:11]([CH3:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]([CH2:14][CH2:15][N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C:7]2=[O:13].[F:25][C:26]1[CH:27]=[C:28]([CH2:36][C:37](O)=[O:38])[CH:29]=[CH:30][C:31]=1[C:32]([F:35])([F:34])[F:33].C(N(CC)C(C)C)(C)C.CN(C)C=O>>[F:25][C:26]1[CH:27]=[C:28]([CH2:36][C:37]([NH:1][C:2]2[C:11]([CH3:12])=[CH:10][CH:9]=[C:8]3[C:3]=2[CH:4]=[CH:5][N:6]([CH2:14][CH2:15][N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:21])([CH3:20])[CH3:22])[C:7]3=[O:13])=[O:38])[CH:29]=[CH:30][C:31]=1[C:32]([F:34])([F:35])[F:33]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 27375913-Fluoro-4-(trifluoromethyl)phenylacetic acidHCID 66649213tert-Butyl 2-(5-amino-6-methyl-1-oxoisoquinolin-2(1H)-yl)ethyl(methyl)carbamate

Product 1

HCID 86624819tert-Butyl 2-(5-(2-(3-fluoro-4-(trifluoromethyl)phenyl)acetamido)-6-methyl-1-oxoisoquinolin-2(1H)-yl)ethyl(methyl)carbamate

Conditions

Temperature
45 °C

Procedure

A reaction vial was charged with tert-butyl 2-(5-amino-6-methyl-1-oxoisoquinolin-2(1H)-yl)ethyl(methyl)carbamate (150 mg, 0.00041 mol), 2-(3-fluoro-4-(trifluoromethyl)phenyl)acetic acid (200 mg, 0.0009 mol), N,N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (700 mg, 0.002 mol), N,N-diisopropylethylamine (0.3 mL, 0.002 mol), N,N-dimethylformamide (4 mL, 0.05 mol) and the reaction was stirred at 45° C. overnight. The reaction was then quenched with water, extracted with warm ethyl acetate, and the solvent removed under reduced pressure. The residue was purified by flash chromatography and then by reversed phase preparative HPLC to afford the product as an off white solid.

Workup

  1. customA reaction
  2. customThe reaction was then quenched with water
  3. extractionextracted with warm ethyl acetate
  4. customthe solvent removed under reduced pressure
  5. customThe residue was purified by flash chromatography
  6. customby reversed phase preparative HPLC to afford the product as an off white solid

Sources & evidence

ORD record
ord-e941cac8ee084073844aec137cf43944
Source dataset
uspto-grants-2012_01
Patent number
US08093265B2

Reaction notes

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