Dimethylformamide → (R)-2-(5-(2-(3-Fluoro-4-(trifluoromethyl)phenyl)acetamido)-6-methyl-1-oxoisoquinolin-2(1H)-yl)propyl acetate

HRID 418517Notes

Reaction equation

HRID 418517 reaction equation
[C:1]([O:4][CH2:5][C@H:6]([N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH3:19])[C:14]=2[NH2:18])[C:9]1=[O:20])[CH3:7])(=[O:3])[CH3:2].[F:21][C:22]1[CH:23]=[C:24]([CH2:32][C:33](O)=[O:34])[CH:25]=[CH:26][C:27]=1[C:28]([F:31])([F:30])[F:29].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.CN(C)C=O>>[C:1]([O:4][CH2:5][C@H:6]([N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH3:19])[C:14]=2[NH:18][C:33](=[O:34])[CH2:32][C:24]2[CH:25]=[CH:26][C:27]([C:28]([F:29])([F:30])[F:31])=[C:22]([F:21])[CH:23]=2)[C:9]1=[O:20])[CH3:7])(=[O:3])[CH3:2]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 27375913-Fluoro-4-(trifluoromethyl)phenylacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59515683(R)-2-(5-amino-6-methyl-1-oxoisoquinolin-2(1H)-yl)propyl acetate

Product 1

HCID 59515877(R)-2-(5-(2-(3-Fluoro-4-(trifluoromethyl)phenyl)acetamido)-6-methyl-1-oxoisoquinolin-2(1H)-yl)propyl acetate

Conditions

Temperature
45 °C

Procedure

A round bottom flask was charged with (R)-2-(5-amino-6-methyl-1-oxoisoquinolin-2(1H)-yl)propyl acetate (175 mg, 0.000638 mol), 2-(3-fluoro-4-(trifluoromethyl)phenyl)acetic acid (210 mg, 0.00096 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (610 mg, 0.0016 mol), N,N-diisopropylethylamine (0.28 mL, 0.0016 mol) and N,N-dimethylformamide (8 mL, 0.1 mol). The reaction mixture was stirred at 45° C. for 24 hours. The reaction was quenched with water and extracted with ethyl acetate, washed with sodium bicarbonate, brine, and dried. The solvent was removed under reduced pressure and the residue was purified by flash chromatography to afford the product as a light yellow oil.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with ethyl acetate
  3. washwashed with sodium bicarbonate, brine
  4. customdried
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-69459c7411a34bea8667d5c3143ac58a
Source dataset
uspto-grants-2012_01
Patent number
US08093265B2

Reaction notes

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