Cesium carbonate → (2R)-2-[[(4-Chlorophenyl)sulfonyl][(4-cyano-2-fluorophenyl)methyl]amino]-5,5,5-trifluoropentanamide

HRID 1803739Notes

Reaction equation

HRID 1803739 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C@H:12]([CH2:16][CH2:17][C:18]([F:21])([F:20])[F:19])[C:13]([NH2:15])=[O:14])(=[O:10])=[O:9])=[CH:4][CH:3]=1.Br[CH2:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][C:25]=1[F:32].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([C@H:12]([CH2:16][CH2:17][C:18]([F:21])([F:19])[F:20])[C:13]([NH2:15])=[O:14])[CH2:23][C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][C:25]=2[F:32])(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27831494-(Bromomethyl)-3-fluorobenzonitrileHCID 56953106HCID 56953106, compound

Product 1

HCID 56953105(2R)-2-[[(4-Chlorophenyl)sulfonyl][(4-cyano-2-fluorophenyl)methyl]amino]-5,5,5-trifluoropentanamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-2-(4-chlorophenylsulfonamido)-5,5,5-trifluoropentanamide (6.88 g, 20.0 mmol) and 4-(bromomethyl)-3-fluorobenzonitrile (6.43 g, 30 mmol) in DMF (35 mL) was added anhydrous Cs2CO3 (19.56 g, 60 mmol). The resulting mixture was stirred at room temperature for 45 min. and then diluted with EtOAc (200 mL), washed with water (100 mL×4) and dried over Na2SO4. The product was purified by Biotage (40+M column, 3% to 80% EtOAc in hexanes, 651 mL). The title compound was obtained as a white solid (6.50 g, 68.1% yield). 1H NMR (DMSO-d6, 400 MHz) δ 7.80-7.88 (m, 3H), 7.70-7.75 (m, 2H), 7.67 (d, 2H, J=8), 7.60 (s, 1H), 7.26 (s, 1H), 4.99 (d, 1H, J=16), 4.68 (d, 1H, J=16), 4.14 (t, 1H, J=8), 1.99-2.17 (m, 2H), 1.80-1.94 (m, 1H), 1.40-1.56 (m, 1H). LC/MS M+H 478.14, 94%.

Workup

  1. washwashed with water (100 mL×4)
  2. dry with materialdried over Na2SO4
  3. customThe product was purified by Biotage (40+M column, 3% to 80% EtOAc in hexanes, 651 mL)

Sources & evidence

ORD record
ord-ec2c346cf6834170b93e6fdfe6e00f33
Source dataset
uspto-grants-2013_01
Patent number
US08350084B2

Reaction notes

Loading…