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

HRID 573248Notes

Reaction equation

HRID 573248 reaction equation
[CH:1]1([OH:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C1C=CC=CN=1)C.C(N=C=NCCCN(C)C)C.[F:28][CH:29]([F:55])[C:30]1[CH:34]=[C:33]([CH:35]([F:37])[F:36])[N:32]([CH2:38][C:39]([N:41]2[CH2:46][CH2:45][CH:44]([C:47]3[S:48][CH:49]=[C:50]([C:52](O)=[O:53])[N:51]=3)[CH2:43][CH2:42]2)=[O:40])[N:31]=1>ClCCl.O>[F:55][CH:29]([F:28])[C:30]1[CH:34]=[C:33]([CH:35]([F:36])[F:37])[N:32]([CH2:38][C:39]([N:41]2[CH2:42][CH2:43][CH:44]([C:47]3[S:48][CH:49]=[C:50]([C:52]([O:7][CH:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)=[O:53])[N:51]=3)[CH2:45][CH2:46]2)=[O:40])[N:31]=1

Participants

7

Reactant 4

HCID 7966CyclohexanolHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 218852-DimethylaminopyridineHCID 44469184HCID 44469184, compound

Product 1

HCID 66911494Cyclohexyl 2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

At room temperature, cyclohexanol (2.17 g), dimethylaminopyridine (0.20 g) and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide (3.35 g) are added to a solution of 2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazole-4-carboxylic acid (III-1, 7.00 g) in dichloromethane (80 ml). The mixture is stirred overnight, and water is then added. The aqueous phase is separated off and extracted with ethyl acetate. The combined organic phases are dried with sodium sulfate. The solid is filtered off and the solvent is removed by distillation. The residue is purified chromatographically. This gives cyclohexyl 2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazole-4-carboxylate (2.83 g, 34%).

Workup

  1. customThe aqueous phase is separated off
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic phases are dried with sodium sulfate
  4. filtrationThe solid is filtered off
  5. customthe solvent is removed by distillation
  6. customThe residue is purified chromatographically

Sources & evidence

ORD record
ord-89465202692d4b35ac70dc386a35f2b3
Source dataset
uspto-grants-2015_05
Patent number
US09029549B2

Reaction notes

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