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

HRID 1047322Notes

Reaction equation

HRID 1047322 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 444691842-(1-{[3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazole-4-carboxylic acid

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-fce3b5ea6e4a4cb5979fca04b85b50e2
Source dataset
uspto-grants-2013_10
Patent number
US08569509B2

Reaction notes

Loading…