Diisopropylethylamine → HCID 44593549, compound

HRID 886726Notes

Reaction equation

HRID 886726 reaction equation
[CH3:1][S:2]([C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O)(=[O:4])=[O:3].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)O.[NH2:38][C:39]1[N:43]([C:44]2[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=2)[N:42]=[CH:41][C:40]=1[C:51]([NH:53][CH2:54][C:55]([CH2:61][NH:62][CH2:63][CH3:64])([OH:60])[C:56]([F:59])([F:58])[F:57])=[O:52]>CN(C)C=O>[NH2:38][C:39]1[N:43]([C:44]2[CH:45]=[CH:46][C:47]([F:50])=[CH:48][CH:49]=2)[N:42]=[CH:41][C:40]=1[C:51]([NH:53][CH2:54][C:55]([CH2:61][N:62]([CH2:63][CH3:64])[C:7]([C:6]1[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=1[S:2]([CH3:1])(=[O:3])=[O:4])=[O:9])([OH:60])[C:56]([F:59])([F:58])[F:57])=[O:52]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2843422-Methanesulfonylbenzoic acidHCID 21864398Tetramethyluronium hexafluorophosphateHCID 59187223HCID 59187223, compound

Product 1

HCID 44593549HCID 44593549, compoundYield 91.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(Methylsulphonyl)benzoic acid (0.204 g, 1.017 mmol) was dissolved in dry dimethylformamide before diisopropylethylamine (0.531 ml, 3.05 mmol) was added. O-7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (0.464 g, 1.22 mmol) was added and the reaction stirred for 10 minutes. The reaction mixture was cooled in ice and then 5-amino-N-{2-[(ethylamino)methyl]-3,3,3-trifluoro-2-hydroxypropyl}-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide (0.46 g, 1.118 mmol, 1.1 equiv) was added (washed in with dimethylformamide) (total volume of dimethylformamide used 2.5 ml). The reaction was then stirred at room temperature overnight. The reaction mixture was then concentrated under reduced pressure and the residue was partitioned between dichloromethane and water. The product was extracted into dichloromethane and concentrated under reduced pressure. The crude product was purified on silica (50 g) with a 0-100% ethyl acetate:dichloromethane over 40 minutes as gradient to give the title compound (0.53 g).

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was cooled in ice
  3. wash(washed in with dimethylformamide) (total volume of dimethylformamide used 2.5 ml)
  4. stirringThe reaction was then stirred at room temperature overnight
  5. concentrationThe reaction mixture was then concentrated under reduced pressure
  6. customthe residue was partitioned between dichloromethane and water
  7. extractionThe product was extracted into dichloromethane
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified on silica (50 g) with a 0-100% ethyl acetate

Sources & evidence

ORD record
ord-b0081aba5a6143118935abf3a58ad5af
Source dataset
uspto-grants-2012_08
Patent number
US08247377B2

Reaction notes

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