Triphenylphosphine → (2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)acrylamide

HRID 2192936Notes

Reaction equation

HRID 2192936 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[CH:28]1([C:31]2[CH:32]=[C:33](/[C:43](=[CH:47]\[CH:48]3[CH2:53][CH2:52][O:51][CH2:50][CH2:49]3)/[C:44]([OH:46])=O)[CH:34]=[CH:35][C:36]=2[S:37]([CH:40]2[CH2:42][CH2:41]2)(=[O:39])=[O:38])[CH2:30][CH2:29]1.[CH3:54][N:55]1[CH:59]=[CH:58][C:57]([NH2:60])=[N:56]1>ClCCl.N1C=CC=CC=1.O>[CH:28]1([C:31]2[CH:32]=[C:33](/[C:43](=[CH:47]\[CH:48]3[CH2:49][CH2:50][O:51][CH2:52][CH2:53]3)/[C:44]([NH:60][C:57]3[CH:58]=[CH:59][N:55]([CH3:54])[N:56]=3)=[O:46])[CH:34]=[CH:35][C:36]=2[S:37]([CH:40]2[CH2:41][CH2:42]2)(=[O:38])=[O:39])[CH2:30][CH2:29]1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 1372541-Methyl-3-aminopyrazoleHCID 59571023(2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)acrylic acid

Product 1

HCID 59570897(2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)acrylamideYield 80.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a solution of triphenylphosphine (131 mg) in dichloromethane (2 mL) was added N-bromosuccinimide (89 mg) under ice-cooling, followed by stirring for 15 minutes under ice-cooling. A solution of (2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)acrylic acid (100 mg) in dichloromethane (1 mL) was added thereto, followed by stirring at room temperature for 30 minutes. A solution of 1-methyl-1H-pyrazol-3-amine (39 mg) in dichloromethane (1 mL) and pyridine (0.086 mL) were added thereto at room temperature, followed by stirring at room temperature for 15 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was sequentially washed with 1 M hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution, and saturated brine, and dried over anhydrous magnesium sulfate. The crude product obtained by concentration was purified by silica gel column chromatography to obtain (2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)acrylamide (97 mg).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringby stirring at room temperature for 30 minutes
  4. customat room temperature
  5. stirringby stirring at room temperature for 15 hours
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe organic layer was sequentially washed with 1 M hydrochloric acid
  8. dry with materiala saturated aqueous sodium hydrogen carbonate solution, and saturated brine, and dried over anhydrous magnesium sulfate
  9. customThe crude product obtained by concentration
  10. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-7fbaa6e5e0da48f7ab27e7fef3a72ac1
Source dataset
uspto-grants-2012_12
Patent number
US08329707B2

Reaction notes

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