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

HRID 2261908Notes

Reaction equation

HRID 2261908 reaction equation
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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-d8d041948e1c41229cc0aa09741e7015
Source dataset
uspto-grants-2010_12
Patent number
US07847100B2

Reaction notes

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