Ethyl 4,4,4-trifluoroacetoacetate → HCID 178516598, compound

HRID 1747506Notes

Reaction equation

[F:1][C:2]([F:12])([F:11])[C:3](=[O:10])[CH2:4][C:5]([O:7]CC)=O.[F:13][CH:14]([F:34])[O:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[CH2:27][CH2:26][CH:25]([C:28]3[CH:32]=[C:31]([NH2:33])[NH:30][N:29]=3)[CH2:24][CH2:23]2)=[CH:18][CH:17]=1>C(O)(=O)C>[F:34][CH:14]([F:13])[O:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[CH2:27][CH2:26][CH:25]([C:28]3[C:32]4[C:3]([OH:10])([C:2]([F:1])([F:11])[F:12])[CH2:4][C:5](=[O:7])[NH:33][C:31]=4[NH:30][N:29]=3)[CH2:24][CH2:23]2)=[CH:18][CH:17]=1

Participants

Conditions

Temperature: 60 °C

Procedure

Ethyl trifluoroacetoacetate (5.64 mL, 38.5 mmol) was added to a solution of 3-{1-[4-(difluoromethoxy)phenyl]piperidin-4-yl}-1H-pyrazol-5-amine (2.97 g, 9.63 mmol) produced in Reference Example 72 in acetic acid (52 mL), and the mixture was stirred at 60° C. for 3 hours. The reaction solution was cooled to room temperature, and the solvent was distilled off under reduced pressure, followed by azeotropy with toluene twice. The obtained residue was purified by silica gel column chromatography [NH-silica gel column, elute: hexane/ethyl acetate=100/0-0/100 (gradient)] and further purified by silica gel column chromatography [elute: hexane/ethyl acetate=100/0-40/60 (gradient)] to obtain the title compound (1.84 g, yield: 43%).

Workup

temperatureThe reaction solution was cooled to room temperature
distillationthe solvent was distilled off under reduced pressure
customThe obtained residue was purified by silica gel column chromatography [NH-silica gel column, elute: hexane/ethyl acetate=100/0-0/100 (gradient)]
customfurther purified by silica gel column chromatography [elute: hexane/ethyl acetate=100/0-40/60 (gradient)]

Sources & evidence

ORD record: ord-4d609e43a100418c89378d820fa9c117
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09150575B2

Reaction notes

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