Water → HCID 68296981, compound

HRID 70802Notes

Reaction equation

HRID 70802 reaction equation
[F:1][CH:2]([F:33])[C:3]1[CH:7]=[C:6]([CH:8]([F:10])[F:9])[N:5]([CH2:11][C:12]([N:14]2[CH2:19][CH2:18][CH:17]([C:20]3[S:21][CH:22]=[C:23]([C:25]4[CH2:29][CH:28]([C:30]([OH:32])=[O:31])[O:27][N:26]=4)[N:24]=3)[CH2:16][CH2:15]2)=[O:13])[N:4]=1.[Cl:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH:36]1O.Cl.C(N=C=NCCCN(C)C)C.O>ClCCl.CN(C)C1C=CN=CC=1>[F:33][CH:2]([F:1])[C:3]1[CH:7]=[C:6]([CH:8]([F:10])[F:9])[N:5]([CH2:11][C:12]([N:14]2[CH2:19][CH2:18][CH:17]([C:20]3[S:21][CH:22]=[C:23]([C:25]4[CH2:29][CH:28]([C:30]([O:32][CH:36]5[CH2:37][CH2:38][CH2:39][CH2:40][CH:35]5[Cl:34])=[O:31])[O:27][N:26]=4)[N:24]=3)[CH2:16][CH2:15]2)=[O:13])[N:4]=1

Participants

7

Reactant 4

HCID 962WaterHCID 152742-ChlorocyclohexanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 683144523-[2-(1-{[3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazole-5-carboxylic acid

Product 1

HCID 68296981HCID 68296981, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazole-5-carboxylic acid (E, 160 mg) in dichloromethane (5 ml) are added, at room temperature, 2-chlorocyclohexanol (57 mg), 4-dimethylaminopyridine (4 mg) and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (94 mg). The mixture is stirred overnight, and water is then added. The aqueous phase is removed and extracted with ethyl acetate. The combined organic phases are dried over sodium sulfate. The solids are filtered off and the solvent is distilled off. The residue is purified by chromatography. This gives 2-chlorocyclohexyl 3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazole-5-carboxylate (100 mg, 50%).

Workup

  1. customThe aqueous phase is removed
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic phases are dried over sodium sulfate
  4. filtrationThe solids are filtered off
  5. distillationthe solvent is distilled off
  6. customThe residue is purified by chromatography

Sources & evidence

ORD record
ord-33004f25daeb4eaa95b6c15a34f6c655
Source dataset
uspto-grants-2014_09
Patent number
US08822693B2

Reaction notes

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