Methanol → (R)-N-(6-Cyclopropyl-2-(1-hydroxypropan-2-yl)-1-oxo-1,2-dihydroisoquinolin-5-yl)-2-(3-fluoro-4-(trifluoromethyl)phenyl)acetamide

HRID 1161283Notes

Reaction equation

HRID 1161283 reaction equation
C([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]([CH:33]3[CH2:35][CH2:34]3)[C:14]=2[NH:18][C:19](=[O:32])[CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[C:23]([F:31])[CH:22]=2)[C:9]1=[O:36])[CH3:7])(=O)C.C(=O)([O-])[O-].[K+].[K+].CO>O>[CH:33]1([C:13]2[C:14]([NH:18][C:19](=[O:32])[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]([F:28])([F:30])[F:29])=[C:23]([F:31])[CH:22]=3)=[C:15]3[C:10](=[CH:11][CH:12]=2)[C:9](=[O:36])[N:8]([C@H:6]([CH3:7])[CH2:5][OH:4])[CH:17]=[CH:16]3)[CH2:35][CH2:34]1

Participants

5

Reactant 3

HCID 887MethanolHCID 11430Potassium CarbonateHCID 59515703(R)-2-(6-Cyclopropyl-5-(2-(3-fluoro-4-(trifluoromethyl)phenyl)acetamido)-1-oxoisoquinolin-2(1H)-yl)propyl acetate

Product 1

HCID 25013921(R)-N-(6-Cyclopropyl-2-(1-hydroxypropan-2-yl)-1-oxo-1,2-dihydroisoquinolin-5-yl)-2-(3-fluoro-4-(trifluoromethyl)phenyl)acetamide

Reagents, catalysts & solvents 1

HCID 962WaterCatalyst

Procedure

A round bottom flask was charged with (R)-2-(6-cyclopropyl-5-(2-(3-fluoro-4-(trifluoromethyl)phenyl)acetamido)-1-oxoisoquinolin-2(1H)-yl)propyl acetate (23 mg, 0.000046 mol), potassium carbonate (9.4 mg, 0.000068 mol) and methanol (2 mL, 0.05 mol) and 2 drops of water and the reaction was stirred for 30 minutes. The reaction mixture was then filtered over celite and the solvent removed under reduced pressure. The residue was then purified by preparative HPLC (reverse phase) to get the product as a sticky mass. MS m/z=463.5 (M+H). 1H NMR (400 MHz; Acetone-d) δ 9.02 (s, 1H), 8.03 (d, J=8.15 Hz, 1H), 7.61 (t, J=7.52 Hz, 1H), 7.42 (d, J=5.01 Hz, 1H), 7.39 (s, 1H), 7.24 (d, J=7.52 Hz, 1H), 6.91 (d, J=8.15 Hz, 1H), 6.36 (d, J=8.15 Hz, 1H), 4.99-4.97 (m, 1H), 3.93 (s, 2H), 3.68-3.64 (m, 2H), 2.04-1.94 (m, 1H), 1.24 (d, J=7.32 Hz, 3H), 0.81-0.77 (m, 2H), 0.60-0.56 (m, 2H).

Workup

  1. filtrationThe reaction mixture was then filtered over celite
  2. customthe solvent removed under reduced pressure
  3. customThe residue was then purified by preparative HPLC (reverse phase)
  4. customto get the product as a sticky mass

Sources & evidence

ORD record
ord-d477155425504ceaa7a96741eedcb42c
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

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