4-(Pyridin-4-yloxy)aniline → ethyl (4-{3-tert-butyl-5-[({[4-(pyridin-4-yloxy)phenyl]amino}carbonyl)amino]-1H-pyrazol-1-yl}phenyl)acetate

HRID 221912Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:31])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:16]([NH:17][C:18](OC3C=CC=CC=3)=[O:19])=[CH:15][C:14]([C:27]([CH3:30])([CH3:29])[CH3:28])=[N:13]2)=[CH:8][CH:7]=1)[CH3:2].[N:32]1[CH:37]=[CH:36][C:35]([O:38][C:39]2[CH:45]=[CH:44][C:42]([NH2:43])=[CH:41][CH:40]=2)=[CH:34][CH:33]=1>C1COCC1>[CH2:1]([O:3][C:4](=[O:31])[CH2:5][C:6]1[CH:7]=[CH:8][C:9]([N:12]2[C:16]([NH:17][C:18]([NH:43][C:42]3[CH:41]=[CH:40][C:39]([O:38][C:35]4[CH:36]=[CH:37][N:32]=[CH:33][CH:34]=4)=[CH:45][CH:44]=3)=[O:19])=[CH:15][C:14]([C:27]([CH3:28])([CH3:29])[CH3:30])=[N:13]2)=[CH:10][CH:11]=1)[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of ethyl(4-{3-tert-butyl-5-[(phenoxycarbonyl)amino]-1H-pyrazol-1-yl}phenyl)acetate (3.0 g, 7.12 mmol) and 4-(pyridin-4-yloxy)aniline (1.26 g, 6.78 mmol) in THF (50 mL) was heated at 60° C. overnight. The reaction mixture was cooled to room temperature and then evaporated at reduced pressure to afford a brown syrup, which was purified by MPLC (25:75 to 70:30 EtOAc/hexane). The desired product was obtained as a white solid (2.42 g) in 70% yield. 1H-NMR (CD2Cl2-d2) δ 8.35 (m, 2H), 8.06 (s, 1H), 7.42 (m, 4H), 7.33 (s, 1H), 7.28 (d, J=8.3 Hz, 2H), 6.99 (d, J=8.8 Hz, 2H), 6.88 (d, J=5.8 Hz, 2H), 6.35 (s, 1H), 4.12 (q, J=7.1 Hz, 2H), 3.63 (s, 2H), 1.31 (s, 9H), 1.27 (t, J=7.1 Hz, 3H); MS LC-MS [M+H]+=514.2, RT=2.66 min.

Workup

temperatureThe reaction mixture was cooled to room temperature
customevaporated at reduced pressure
customto afford a brown syrup, which
customwas purified by MPLC (25:75 to 70:30 EtOAc/hexane)

Sources & evidence

ORD record: ord-58cee1e27cd7407bbb304ac00344966c
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08207166B2

Reaction notes

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