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 1161283노트

반응식

HRID 1161283 반응식
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

참가 물질

5

반응물 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

생성물 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

시약·촉매·용매 1

HCID 962Water촉매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-d477155425504ceaa7a96741eedcb42c
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07816371B2

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