Triphenylphosphine → HCID 68670888, compound

HRID 2192951Notes

Reaction equation

HRID 2192951 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]\[C@H:48]3[CH2:68][CH2:67][C:50]4([O:54][C@H:53]([C:55]5[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=5)[C@@H:52]([C:61]5[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=5)[O:51]4)[CH2:49]3)/[C:44](O)=[O:45])[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.[NH2:69][C:70]1[CH:74]=[CH:73][N:72]([C:75]([O:77][C:78]([CH3:81])([CH3:80])[CH3:79])=[O:76])[N:71]=1>ClCCl.O.N1C=CC=CC=1>[CH:28]1([C:31]2[CH:32]=[C:33](/[C:43](=[CH:47]\[C@H:48]3[CH2:68][CH2:67][C:50]4([O:54][C@H:53]([C:55]5[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=5)[C@@H:52]([C:61]5[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=5)[O:51]4)[CH2:49]3)/[C:44]([NH:69][C:70]3[CH:74]=[CH:73][N:72]([C:75]([O:77][C:78]([CH3:81])([CH3:80])[CH3:79])=[O:76])[N:71]=3)=[O:45])[CH:34]=[CH:35][C:36]=2[S:37]([CH:40]2[CH2:41][CH2:42]2)(=[O:39])=[O:38])[CH2:29][CH2:30]1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 51358380tert-Butyl 3-amino-1H-pyrazole-1-carboxylateHCID 59571019HCID 59571019, compound

Product 1

HCID 68670888HCID 68670888, compoundYield 87.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent4×

Procedure

To a solution of triphenylphosphine (300 mg) in dichloromethane (4 mL) was added N-bromosuccinimide (200 mg) under ice-cooling, followed by stirring for 15 minutes under ice-cooling, and a solution of (2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(2R,3R,7S)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]acrylic acid (300 mg) in dichloromethane (3 mL) was then slowly added thereto, followed by stirring at room temperature for 30 minutes. To the reaction mixture was added a solution of tert-butyl 3-amino-1H-pyrazole-1-carboxylate (190 mg) in dichloromethane (3 mL), and further added pyridine (0.1 mL), followed by stirring at room temperature for 3 hours. To the reaction mixture were added water (20 mL) and dichloromethane (20 mL), and the organic layer was sequentially washed with 1 M hydrochloric acid (20 mL) and saturated brine (20 mL), and dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=75:25→60:40) to obtain tert-butyl 3-({(2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(2R,3R,7S)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl] prop-2-enoyl}amino)-1H-pyrazole-1-carboxylate (338 mg) as a colorless amorphous substance. To a solution of tert-butyl 3-({(2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(2R,3R,7S)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]prop-2-enoyl}amino)-1H-pyrazole-1-carboxylate (330 mg) in 1,4-dioxane (3 mL) was added 4 M hydrochloric acid (3 mL), followed by stirring at 50° C. for 3 hours. After leaving it to be cooled at room temperature, 1 M sodium hydroxide (12 mL), saturated brine (20 mL), and dichloromethane (20 mL) were added thereto, the organic layer was dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. To a solution of the residue in ethyl acetate (3 mL) was added 4 M hydrogen chloride/ethyl acetate (0.3 mL), followed by stirring at room temperature for a while, and the solvent was then evaporated under reduced pressure. The obtained colorless solid was purified by silica gel column chromatography (ethyl acetate→chloroform→chloroform/methanol (95/5)) and again purified by silica gel column chromatography (ethyl acetate/methanol 100/0→90/10) to obtain (2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1S)-3-oxocyclopentyl]-N-1H-pyrazol-3-yl acrylamide (100 mg) as a colorless amorphous substance.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringby stirring at room temperature for 30 minutes
  4. stirringby stirring at room temperature for 3 hours
  5. washthe organic layer was sequentially washed with 1 M hydrochloric acid (20 mL) and saturated brine (20 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was then evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=75:25→60:40)

Sources & evidence

ORD record
ord-b9c16ace961242ce88b17c46e9768d6f
Source dataset
uspto-grants-2012_12
Patent number
US08329707B2

Reaction notes

Loading…