Diisopropylamine → N-[(1R)-1-(4-fluorophenyl)ethyl]-3-(5-formyl-2-furyl)-5-[methyl (methylsulfonyl)amino]benzamide

HRID 2261908노트

반응식

HRID 2261908 반응식
Br[C:2]1[CH:3]=[C:4]([CH:17]=[C:18]([N:20]([CH3:25])[S:21]([CH3:24])(=[O:23])=[O:22])[CH:19]=1)[C:5]([NH:7][C@@H:8]([C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1)[CH3:9])=[O:6].[CH:26]([C:28]1[O:32][C:31](B(O)O)=[CH:30][CH:29]=1)=[O:27].C1C=C(S([O-])(=O)=O)C=C(P(C2C=CC=C(S([O-])(=O)=O)C=2)C2C=CC=C(S([O-])(=O)=O)C=2)C=1.[Na+].[Na+].[Na+].C(NC(C)C)(C)C>CN(C=O)C>[F:16][C:13]1[CH:14]=[CH:15][C:10]([C@H:8]([NH:7][C:5](=[O:6])[C:4]2[CH:17]=[C:18]([N:20]([CH3:25])[S:21]([CH3:24])(=[O:23])=[O:22])[CH:19]=[C:2]([C:31]3[O:32][C:28]([CH:26]=[O:27])=[CH:29][CH:30]=3)[CH:3]=2)[CH3:9])=[CH:11][CH:12]=1

참가 물질

6

반응물 4

HCID 7912DiisopropylamineHCID 27343555-Formylfuran-2-boronic acidHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)HCID 589900843-bromo-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzamide

생성물 1

HCID 58990159N-[(1R)-1-(4-fluorophenyl)ethyl]-3-(5-formyl-2-furyl)-5-[methyl (methylsulfonyl)amino]benzamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of Intermediate X (0.280 g, 0.65 mmol) and (5-formyl-2-furyl)boronic acid (0.0912 g, 0.65 mmol) in 5 mL degassed DMF was added TPPTS (0.111 g, 0.20 mmol) Pd(OAc)2 (0.015 g, 0.07 mmol) and diisopropylamine (0.066 g, 0.65 mmol). After 15 h at rt, the reaction was diluted with satd. aqueous NaHCO3 and EtOAc, and the layers were separated. The organics were washed with brine, dried over Na2SO4, filtered and concentrated. Purification by normal phase chromatography (50->100% EtOAc/hexanes) afforded the desired coupled adduct. 1H NMR (400 MHz, CDCl3) δ 9.67 (s, 1H), 8.09 (m, 1H), 7.95 (m, 1H), 7.84 (m, 1H), 7.41-7.34 (m, 3H), 7.08 (m, 2H), 6.99 (d, J=5.9 Hz, 1H), 6.54 (d, J=7.5 Hz, 1H), 5.31 (m, 1H), 3.40 (s, 3H), 2.89 (s, 3H), 1.65 (d, J=7.0 Hz, 3H). LCMS [M+H]+=445.

후처리

  1. additionthe reaction was diluted with satd
  2. customaqueous NaHCO3 and EtOAc, and the layers were separated
  3. washThe organics were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by normal phase chromatography (50->100% EtOAc/hexanes)
  8. customafforded the

출처 및 근거

ORD 기록
ord-d8d041948e1c41229cc0aa09741e7015
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07847100B2

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