Diisopropylethylamine → 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[5-fluoro-2-(3-methyl-benzo[d]isoxazol-6-yloxy)-benzyl]-urea

HRID 1897464Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[CH:20]=[CH:19][C:14]3[C:15]([CH3:18])=[N:16][O:17][C:13]=3[CH:12]=2)=[C:6]([CH:9]=1)[CH2:7][NH2:8].FC(F)(F)C[O:24][C:25](=O)[NH:26][C:27]1[N:28]([C:36]2[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][CH:37]=2)[N:29]=[C:30]([C:32]([CH3:35])([CH3:34])[CH3:33])[CH:31]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[C:32]([C:30]1[CH:31]=[C:27]([NH:26][C:25]([NH:8][CH2:7][C:6]2[CH:9]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[O:10][C:11]2[CH:20]=[CH:19][C:14]3[C:15]([CH3:18])=[N:16][O:17][C:13]=3[CH:12]=2)=[O:24])[N:28]([C:36]2[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][CH:37]=2)[N:29]=1)([CH3:35])([CH3:33])[CH3:34]

Participants

Conditions

Temperature: 75 °C

Procedure

5-Fluoro-2-(3-methyl-benzo[d]isoxazol-6-yloxy)-benzylamine (9v) (60 mg, 0.22 mmol), (5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trifluoro-ethyl ester (12v) (89 mg, 0.22 mmol) and diisopropylethylamine (0.058 mL, 0.33 mmol) were combined in DMF (2 mL) and heated at 75° C. for 3 hours. The reaction was cooled and concentrated in vacuo and purified by column chromatography (silica, 30 to 40% EtOAc/hexanes) to provide compound (10v) (90 mg, 77% yield). 1H NMR (400 MHz, CDCl3) δ 7.51 (d, J=8.6 Hz, 1H), 7.30 (d, J=8.6 Hz, 2H), 7.20 (d, J=7.8 Hz, 2H), 7.02-6.88 (m, 5H), 6.15 (s, 1H), 5.99 (s, 1H), 5.28 (t, J=7.6 Hz, 1H), 4.36 (d, J=5.5 Hz, 2H), 2.53 (s, 3H), 2.36 (s, 3H), 1.31 (s, 9H); MS (ESI+) m/z 528 (M+H) detected; HPLC (5 to 95%) 3.49 min.

Workup

temperatureThe reaction was cooled
concentrationconcentrated in vacuo
custompurified by column chromatography (silica, 30 to 40% EtOAc/hexanes)

Sources & evidence

ORD record: ord-d5e04a65f8774b6196c14cfb8d688b04
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08518983B2

Reaction notes

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