N-bromobutanimide → N-{3-[5-(2-Chloro-4-pyrimidinyl)-2-(1-pyrrolidinyl)-1,3-thiazol-4-yl]phenyl}-2,6-difluorobenzenesulfonamide

HRID 590012Notes

Reaction equation

HRID 590012 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](/[CH:8]=[C:9](/[C:11]2[CH:12]=[C:13]([NH:17][S:18]([C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])(=[O:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)\O)[CH:5]=[CH:4][N:3]=1.C1C(=O)N(Br)C(=O)C1.[N:37]1([C:42](=[S:44])[NH2:43])[CH2:41][CH2:40][CH2:39][CH2:38]1>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:44][C:42]([N:37]3[CH2:41][CH2:40][CH2:39][CH2:38]3)=[N:43][C:9]=2[C:11]2[CH:12]=[C:13]([NH:17][S:18]([C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])(=[O:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 67184N-bromobutanimideHCID 1559568Pyrrolidine-1-carbothioamideHCID 136176025N-{3-[(Z)-2-(2-Chloro-4-pyrimidinyl)-1-hydroxyethenyl]phenyl}-2,6-difluorobenzenesulfonamide

Product 1

HCID 57989807N-{3-[5-(2-Chloro-4-pyrimidinyl)-2-(1-pyrrolidinyl)-1,3-thiazol-4-yl]phenyl}-2,6-difluorobenzenesulfonamideYield 41.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring suspension of N-{3-[(Z)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]phenyl}-2,6-difluorobenzenesulfonamide (1.0 g, 2.36 mmol, 1.0 eq) in DCM (˜5 mL) was added NBS (0.44 g, 2.48 mmol, 1.05 eq). Upon formation of a red solution (˜10 minutes) the reaction mixture was concentrated to a solid and taken up in dioxane (10 mL). To this solution was added MgCO3 (0.38 g) followed by 1-pyrrolidinecarbothioamide (0.384 g, 2.95 mmol, 1.25 eq). After stirring 3 h, the mixture was quenched with water (50 mL) and 1N HCl (10 mL) and stirred 0.25 h. The mixture was filtered and the resultant solid triturated with EtOAc/Hexanes to give 0.52 g (41%) of the title compound. 1H-NMR (400 MHz, DMSO-d6) δ ppm 11.11 (s, 1H), 8.14 (d, J=5.7 Hz, 1H), 7.65-7.74 (m, 1H), 7.41 (t, J=7.7 Hz, 1H), 7.18-7.29 (m, 5H), 6.44 (d, J=5.5 Hz, 1H), 3.45-3.52 (m, 4H), and 1.98-2.05 (m, 4H).

Workup

  1. concentrationUpon formation of a red solution (˜10 minutes) the reaction mixture was concentrated to a solid
  2. additionTo this solution was added MgCO3 (0.38 g)
  3. customthe mixture was quenched with water (50 mL) and 1N HCl (10 mL)
  4. stirringstirred 0.25 h
  5. filtrationThe mixture was filtered
  6. customthe resultant solid triturated with EtOAc/Hexanes

Sources & evidence

ORD record
ord-d96ca1e137794e79a8496f11d08f246e
Source dataset
uspto-grants-2016_01
Patent number
US09233956B2

Reaction notes

Loading…