Triethylamine → 1-[4-[4-[4,5-Dihydro-5-(2-fluorophenyl)-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-4,4,4-trifluoro-3-methyl-1-butanone

HRID 1802326Notes

Reaction equation

HRID 1802326 reaction equation
[F:1][C:2]([F:10])([F:9])[CH:3]([CH3:8])[CH2:4][C:5](O)=[O:6].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.Cl.[F:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[CH:37]1[O:41][N:40]=[C:39]([C:42]2[N:43]=[C:44]([CH:47]3[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]3)[S:45][CH:46]=2)[CH2:38]1.C(N(CC)CC)C>ClCCl.CN(C)C1C=CN=CC=1>[F:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[CH:37]1[O:41][N:40]=[C:39]([C:42]2[N:43]=[C:44]([CH:47]3[CH2:52][CH2:51][N:50]([C:5](=[O:6])[CH2:4][CH:3]([CH3:8])[C:2]([F:10])([F:9])[F:1])[CH2:49][CH2:48]3)[S:45][CH:46]=2)[CH2:38]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 1361744,4,4-Trifluoro-3-methylbutanoic acidHCID 666183564-[4-[5-(2-Fluorophenyl)-4,5-dihydro-3-isoxazolyl)-2-thiazolyl]piperidine hydrochloride2×

Product 1

HCID 666181811-[4-[4-[4,5-Dihydro-5-(2-fluorophenyl)-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-4,4,4-trifluoro-3-methyl-1-butanone

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4,4,4-trifluoro-3-methyl-butanoic acid (64 mg, 0.408 mmol) in dichloromethane (3 mL) was added 1-propanephosphonic acid cyclic anhydride solution (50% in ethyl acetate, 0.5 mL). After stirring for 5 minutes, 4-[4-[5-(2-fluorophenyl)-4,5-dihydro-3-isoxazolyl)-2-thiazolyl]piperidine hydrochloride (i.e. the product of Step C) (150 mg, 0.408 mmol), triethylamine (0.1 mL) and 4-dimethylaminopyridine (5 mg) were sequentially added The reaction mixture was stirred for 3 h, and then concentrated under reduced pressure. The resulting material was purified by column chromatography on silica gel to provide the title compound, a compound of the present invention, as an oil (151 mg).

Workup

  1. stirringwas stirred for 3 h
  2. concentrationconcentrated under reduced pressure
  3. customThe resulting material was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-2f77f91f7895406e8cc25669c13f7a53
Source dataset
uspto-grants-2013_01
Patent number
US08349870B2

Reaction notes

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