3-Aminopropionitrile → HCID 57990043, compound

HRID 239551Notes

Reaction equation

HRID 239551 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[N:10][C:9]=2[C:17]2[C:18]([F:35])=[C:19]([NH:23][S:24]([C:27]3[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:28]=3[F:34])(=[O:26])=[O:25])[CH:20]=[CH:21][CH:22]=2)[CH:5]=[CH:4][N:3]=1.[NH2:36][CH2:37][CH2:38][C:39]#[N:40].[F-].[Cs+]>CS(C)=O.O>[C:37]([CH2:38][CH2:39][NH:40][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([C:13]([CH3:14])([CH3:15])[CH3:16])=[N:10][C:9]=2[C:17]2[C:18]([F:35])=[C:19]([NH:23][S:24]([C:27]3[C:28]([F:34])=[CH:29][CH:30]=[CH:31][C:32]=3[F:33])(=[O:25])=[O:26])[CH:20]=[CH:21][CH:22]=2)[CH:5]=[CH:4][N:3]=1)#[N:36]

Participants

6

Reactant 3

HCID 16473-AminopropionitrileHCID 25953Cesium fluorideHCID 57989782N-(3-(5-(2-chloro-4-pyrimidinyl)-2-(1,1-diethylethyl)-1,3-thiazol-4-yl)-2-fluoraphenyl)-2,6-difluorobenzenesulfonamide

Product 1

HCID 57990043HCID 57990043, compoundYield 13.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

A 5 mL microwave tube was charged with N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (250 mg, 0.464 mmol) and 3-aminopropionitrile (163 mg, 2.319 mmol) and CsF (70.5 mg, 0.464 mmol) in dimethyl sulfoxide (3.00 mL) to give a yellow solution at rt under nitrogen. The sealed reaction mixture was microwaved at 90° C. for 30 min. For second time, the sealed reaction mixture was microwaved at 100° C. for 1 h. The reaction was diluted with water and a white solid formed. The reaction was filtered and washed with water. The crude product was chromatographed on silica gel column and eluted with CH2Cl2 with chloroform/methanol/ammonium hydroxide (90:9:1) (5% to 100%) and collected fractions. Water and DCM were added to solid and take to a pH=6 and extracted with DCM (3×). The CH2Cl2 layers were dried over Na2SO4, filtered, and concentrated to obtain N-{3-[5-{2-[(2-cyanoethyl)amino]-4-pyrimidinyl}-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (35 mg, 12%). MS (ESI): 573 [M+H]+.

Workup

  1. customto give a yellow solution at rt under nitrogen
  2. customThe sealed reaction mixture
  3. customwas microwaved at 90° C. for 30 min
  4. customFor second time, the sealed reaction mixture
  5. customwas microwaved at 100° C. for 1 h
  6. customa white solid formed
  7. filtrationThe reaction was filtered
  8. washwashed with water
  9. customThe crude product was chromatographed on silica gel column
  10. washeluted with CH2Cl2 with chloroform/methanol/ammonium hydroxide (90:9:1) (5% to 100%)
  11. customcollected fractions
  12. additionWater and DCM were added to solid
  13. extractionextracted with DCM (3×)
  14. dry with materialThe CH2Cl2 layers were dried over Na2SO4
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-a2dc0fed26ea4c6b9cff737b852f4e86
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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