Triethylamine → 1-[4-[4-[4,5-Dihydro-5-(2-fluorophenyl)-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-4-pentyn-1-one
Reaction equation
[C:1]([OH:7])(=O)[CH2:2][CH2:3][C:4]#[CH:5].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.Cl.[F:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[CH:34]1[O:38][N:37]=[C:36]([C:39]2[N:40]=[C:41]([CH:44]3[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]3)[S:42][CH:43]=2)[CH2:35]1.C(N(CC)CC)C>ClCCl.CN(C)C1C=CN=CC=1>[F:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[CH:34]1[O:38][N:37]=[C:36]([C:39]2[N:40]=[C:41]([CH:44]3[CH2:49][CH2:48][N:47]([C:1](=[O:7])[CH2:2][CH2:3][C:4]#[CH:5])[CH2:46][CH2:45]3)[S:42][CH:43]=2)[CH2:35]1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of 4-pentynoic 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, Example 6) (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 (142 mg).
Workup
- stirringThe reaction mixture was stirred for 3 h
- concentrationconcentrated under reduced pressure
- customThe resulting material was purified by column chromatography on silica gel
Sources & evidence
- ORD record
- ord-d6169affe2d845d6a79a20d49fe36848
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08349870B2
Reaction notes
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