Diisopropylethylamine → Cyclohexyl 2-(1-{[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazole-4-carboxylate

HRID 1047334Notes

Reaction equation

HRID 1047334 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]([CH2:12][C:13]([OH:15])=O)[N:4]=1.CCN(C(C)C)C(C)C.[Cl-].[CH:28]1([O:34][C:35]([C:37]2[N:38]=[C:39]([CH:42]3[CH2:47][CH2:46][NH2+:45][CH2:44][CH2:43]3)[S:40][CH:41]=2)=[O:36])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>ClCCl>[F:16][C:2]([F:1])([F:17])[C:3]1[CH:7]=[C:6]([C:8]([F:9])([F:10])[F:11])[N:5]([CH2:12][C:13]([N:45]2[CH2:44][CH2:43][CH:42]([C:39]3[S:40][CH:41]=[C:37]([C:35]([O:34][CH:28]4[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]4)=[O:36])[N:38]=3)[CH2:47][CH2:46]2)=[O:15])[N:4]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 669115194-{4-[(Cyclohexyloxy)carbonyl]-1,3-thiazol-2-yl}piperidinium chlorideHCID 866474523,5-bis-(trifluoromethyl)-1H-pyrazole-1-acetic acid

Product 1

HCID 44468373Cyclohexyl 2-(1-{[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

[3,5-Bis(trifluoromethyl)-1H-pyrazol-1-yl]acetic acid (288 mg) and Hünig base (323 mg) are dissolved in dichloromethane (10 ml) and stirred at room temperature for 30 min. 4-{4-[(Cyclohexyloxy)carbonyl]-1,3-thiazol-2-yl}piperidinium chloride (X-1, 330 mg) is added, and the mixture is stirred for a further 5 min before bromo-tris-pyrrolidinophosphonium hexafluorophosphate (559 mg) is added. The reaction mixture is stirred at room temperature overnight. After removal of the solvent under reduced pressure, the residue is purified chromatographically. This gives cyclohexyl 2-(1-{[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazole-4-carboxylate (348 mg, 65%).

Workup

  1. additionis added
  2. stirringThe reaction mixture is stirred at room temperature overnight
  3. customAfter removal of the solvent under reduced pressure
  4. customthe residue is purified chromatographically

Sources & evidence

ORD record
ord-9bd0b524670c4b4698fd4cb2cd541163
Source dataset
uspto-grants-2013_10
Patent number
US08569509B2

Reaction notes

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