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

HRID 2261908ノート

反応式

HRID 2261908 の反応式
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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-d8d041948e1c41229cc0aa09741e7015
出典データセット
uspto-grants-2010_12
特許番号
US07847100B2

反応ノート

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