1,2-Oxazole-5-carboxylic acid → (S)-N-((6-(5-Cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)ethylamino)pyridin-3-yl)methyl)isoxazole-5-carboxamide

HRID 75898Notes

Reaction equation

[NH2:1][CH2:2][C:3]1[C:4]([NH:19][C@H:20]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH3:21])=[N:5][C:6]([NH:10][C:11]2[CH:15]=[C:14]([CH:16]3[CH2:18][CH2:17]3)[NH:13][N:12]=2)=[C:7]([F:9])[CH:8]=1.[O:29]1[C:33]([C:34](O)=[O:35])=[CH:32][CH:31]=[N:30]1>C(Cl)Cl.C1COCC1>[CH:16]1([C:14]2[NH:13][N:12]=[C:11]([NH:10][C:6]3[N:5]=[C:4]([NH:19][C@H:20]([C:22]4[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=4)[CH3:21])[C:3]([CH2:2][NH:1][C:34]([C:33]4[O:29][N:30]=[CH:31][CH:32]=4)=[O:35])=[CH:8][C:7]=3[F:9])[CH:15]=2)[CH2:18][CH2:17]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (S)-3-(aminomethyl)-N6-(5-cyclopropyl-1H-pyrazol-3-yl)-5-fluoro-N2-(1-(4-fluorophenyl)ethyl)pyridine-2,6-diamine (Example 3, 0.08 g, 0.21 mmol) in DCM-THF mixture (1:1, 4 ml) at 0° C. was added 1.0 eq. of isoxazole-5-carboxylic acid loaded TFP resin. The resulting mixture was stirred vigorously for 1 hour at 0° C., and then filtered. The remaining resin was then washed with DCM-THF (1:1, 2×10 ml portions) for 30 min, and then filtered. The combined filtrates were concentrated, and the resulting oil was purified by column chromatography to give the title compound (3.4 mg, 4%). MS: Calcd.: 479. Found: [M+H]+ 480.

Workup

filtrationfiltered
washThe remaining resin was then washed with DCM-THF (1:1, 2×10 ml portions) for 30 min
filtrationfiltered
concentrationThe combined filtrates were concentrated
customthe resulting oil was purified by column chromatography

Sources & evidence

ORD record: ord-abcd528a29454a7aab01b7417f6e5e41
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835465B2

Reaction notes

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