Diisopropylethylamine → 1-((1S,3R)-5-bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-(2-chloro-6-fluorophenyl)ethan-1-one

HRID 1854572

반응식

HRID 1854572 반응식
[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][C@H:5]([CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[NH:6][C@H:7]2[CH3:12].[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=1[CH2:30][C:31](O)=[O:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>ClCCl>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][C@H:5]([CH2:13][O:14][Si:15]([C:18]([CH3:20])([CH3:19])[CH3:21])([CH3:17])[CH3:16])[N:6]([C:31](=[O:32])[CH2:30][C:24]1[C:25]([F:29])=[CH:26][CH:27]=[CH:28][C:23]=1[Cl:22])[C@H:7]2[CH3:12]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 1234642-Chloro-6-fluorophenylacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118998349(1S,3R)-5-Bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-1,2,3,4-tetrahydroisoquinoline

생성물 1

HCID 1238139441-((1S,3R)-5-bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-(2-chloro-6-fluorophenyl)ethan-1-one수율 81.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Dissolve (1S,3R)-5-bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-1,2,3,4-tetrahydroisoquinoline (1.85 g, 4.99 mmol) and 2-chloro-6-fluorophenylacetic acid (1.04 g, 5.49 mmol) in dichloromethane (50 mL). Add 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (2.85 g, 7.49 mmol) and diisopropylethylamine (1.3 mL, 7.49 mmol) at rt. Stir 3 hours. Add water and extract with dichloromethane three times. Combine the dichloromethane extracts, dry over sodium sulfate, filter, and concentrate under reduced pressure to give a residue. Purify the residue by silica gel chromatography, eluting with ethyl acetate: hexanes (gradient, 5-60%) to give the title compound as a white foam (2.2 g, 4.07 mmol). MS (m/z): 540.2 (M+1).

후처리

  1. customat rt
  2. extractionAdd water and extract with dichloromethane three times
  3. dry with materialdry over sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate under reduced pressure
  6. customto give a residue
  7. customPurify the residue by silica gel chromatography
  8. washeluting with ethyl acetate

출처 및 근거

ORD 기록
ord-9945e35d1470466088d9ad2d9e9f1cb5
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08962654B2

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