Triphenylphosphine → (2E)-3-cyclopentyl-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-{1-[(2S)-2,3-dihydroxypropyl]-1H-pyrazol-3-yl}acrylamide

HRID 2192937Notes

Reaction equation

HRID 2192937 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[CH:28]1(/[CH:33]=[C:34](\[C:38]2[CH:43]=[CH:42][C:41]([S:44]([CH:47]3[CH2:49][CH2:48]3)(=[O:46])=[O:45])=[C:40]([CH:50]3[CH2:52][CH2:51]3)[CH:39]=2)/[C:35](O)=[O:36])[CH2:32][CH2:31][CH2:30][CH2:29]1.CC1(C)[O:58][C@@H:57]([CH2:59][N:60]2[CH:64]=[CH:63][C:62]([NH2:65])=[N:61]2)[CH2:56][O:55]1>ClCCl.N1C=CC=CC=1.O>[CH:28]1(/[CH:33]=[C:34](\[C:38]2[CH:43]=[CH:42][C:41]([S:44]([CH:47]3[CH2:48][CH2:49]3)(=[O:46])=[O:45])=[C:40]([CH:50]3[CH2:51][CH2:52]3)[CH:39]=2)/[C:35]([NH:65][C:62]2[CH:63]=[CH:64][N:60]([CH2:59][C@H:57]([OH:58])[CH2:56][OH:55])[N:61]=2)=[O:36])[CH2:29][CH2:30][CH2:31][CH2:32]1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 57346939(S)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amineHCID 59570950(2E)-3-cyclopentyl-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]acrylic acid

Product 1

HCID 59570952(2E)-3-cyclopentyl-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-{1-[(2S)-2,3-dihydroxypropyl]-1H-pyrazol-3-yl}acrylamideYield 71.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a solution of triphenylphosphine (320 mg) in dichloromethane (10 mL) was added N-bromosuccinimide (217 mg) under ice-cooling, followed by stirring for 15 minutes under ice-cooling. A solution of (2E)-3-cyclopentyl-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]acrylic acid (200 mg) in dichloromethane (10 mL) was added thereto under ice-cooling, followed by stirring at room temperature for 0.5 hour. A solution of 1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-1H-pyrazol-3-amine (142 mg) in dichloromethane (5 mL) and pyridine (0.09 mL) were added thereto at room temperature, followed by stirring at room temperature overnight. Water was added thereto, followed by extraction with ethyl acetate. The organic layer was sequentially washed with 1 M hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated brine, and dried over anhydrous magnesium sulfate. The crude product obtained by concentration was purified by silica gel column chromatography (hexane:ethyl acetate=2:1-1:2). To a solution of the obtained oily substance in THF (15 mL) was added 1 M hydrochloric acid (15 mL), followed by stirring overnight. Saturated brine was added thereto, followed by extraction with a solvent (chloroform:isopropyl alcohol=4:1). The organic layer was dried over anhydrous magnesium sulfate and concentrated. The obtained crude product was purified by silica gel column chromatography (chloroform:methanol=1:0-20:1) to obtain (2E)-3-cyclopentyl-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-{1-[(2S)-2,3-dihydroxypropyl]-1H-pyrazol-3-yl}acrylamide (197 mg) as a white amorphous substance.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. temperatureunder ice-cooling
  4. stirringby stirring at room temperature for 0.5 hour
  5. customat room temperature
  6. stirringby stirring at room temperature overnight
  7. extractionfollowed by extraction with ethyl acetate
  8. washThe organic layer was sequentially washed with 1 M hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe crude product obtained by concentration
  11. customwas purified by silica gel column chromatography (hexane:ethyl acetate=2:1-1:2)
  12. additionTo a solution of the obtained oily substance in THF (15 mL) was added 1 M hydrochloric acid (15 mL)
  13. stirringby stirring overnight
  14. additionSaturated brine was added
  15. extractionfollowed by extraction with a solvent (chloroform:isopropyl alcohol=4:1)
  16. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  17. concentrationconcentrated
  18. customThe obtained crude product
  19. customwas purified by silica gel column chromatography (chloroform:methanol=1:0-20:1)

Sources & evidence

ORD record
ord-da5742c26ed84d6d8cb299f64ef2d897
Source dataset
uspto-grants-2012_12
Patent number
US08329707B2

Reaction notes

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