Diisopropylethylamine → [1-(4-{4-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidine-1-carbonyl)-piperidin-4-yl]-acetic acid methyl ester

HRID 1691939Notes

Reaction equation

HRID 1691939 reaction equation
[N+](C1C=CC([O:10][C:11]([N:13]2[CH2:18][CH2:17][CH:16]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:26]([C:28]4[N:29]=[C:30]([C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=5)[O:31][C:32]=4[C:33]([F:36])([F:35])[F:34])=[O:27])=[CH:21][CH:20]=3)[CH2:15][CH2:14]2)=O)=CC=1)([O-])=O.[CH3:43][O:44][C:45](=[O:53])[CH2:46][CH:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1.C(N(CC)C(C)C)(C)C>CN1CCCC1=O>[CH3:43][O:44][C:45](=[O:53])[CH2:46][CH:47]1[CH2:48][CH2:49][N:50]([C:11]([N:13]2[CH2:18][CH2:17][CH:16]([C:19]3[CH:20]=[CH:21][C:22]([NH:25][C:26]([C:28]4[N:29]=[C:30]([C:37]5[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=5)[O:31][C:32]=4[C:33]([F:35])([F:34])[F:36])=[O:27])=[CH:23][CH:24]=3)[CH2:15][CH2:14]2)=[O:10])[CH2:51][CH2:52]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1515259Methyl 4-piperidineacetateHCID 576520494-{4-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidine-1-carboxylic acid 4-nitro-phenyl ester

Product 1

HCID 66738795[1-(4-{4-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidine-1-carbonyl)-piperidin-4-yl]-acetic acid methyl esterYield 46.8%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidine-1-carboxylic acid 4-nitro-phenyl ester (150 mg, 0.26 mmol) in 1-methyl-pyrrolidin-2-one (10 mL) at room temperature was added piperidin-4-yl-acetic acid methyl ester (0.04 g, 0.25 mmol) followed by N,N-diisopropylethylamine (0.14 mL, 0.8 mmol). The mixture was stirred in a 90° C. oil bath overnight. The mixture was blown to dryness and the crude was purified by flash chromatography (Merck silica gel 60, 230-400 mesh, gradient elution with 0%-60% ethyl acetate in hexane) to give [1-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidine-1-carbonyl)-piperidin-4-yl]-acetic acid methyl ester (70 mg). LCMS calcd for C31H33F3N4O5 (m/e) 598, obsd 599 (M+H).

Workup

  1. customthe crude was purified by flash chromatography (Merck silica gel 60, 230-400 mesh, gradient elution with 0%-60% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-7d50ed917e65461c9f8441852a232744
Source dataset
uspto-grants-2012_04
Patent number
US08153644B2

Reaction notes

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