Diethyl (4-{[4-({7-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate → Diethyl (4-{[4-{[4-bromo-5-fluoro-2-(methylcarbamoyl)phenyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

HRID 2279731Notes

Reaction equation

HRID 2279731 reaction equation
OCCCN1C=C(C2C=CC(N[C:22]3[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][N:25]=[C:24]([NH:32][C:33]4[CH:47]=[CH:46][C:36]([CH2:37][P:38](=[O:45])([O:42][CH2:43][CH3:44])[O:39][CH2:40][CH3:41])=[CH:35][C:34]=4[O:48][CH3:49])[N:23]=3)=C3C=2CN(C)C3=O)C=N1.[NH2:50][C:51]1[CH:60]=[C:59]([F:61])[C:58]([Br:62])=[CH:57][C:52]=1[C:53]([NH:55][CH3:56])=[O:54]>>[Br:62][C:58]1[C:59]([F:61])=[CH:60][C:51]([NH:50][C:26]2[C:27]([C:28]([F:29])([F:30])[F:31])=[CH:22][N:23]=[C:24]([NH:32][C:33]3[CH:47]=[CH:46][C:36]([CH2:37][P:38](=[O:45])([O:42][CH2:43][CH3:44])[O:39][CH2:40][CH3:41])=[CH:35][C:34]=3[O:48][CH3:49])[N:25]=2)=[C:52]([C:53](=[O:54])[NH:55][CH3:56])[CH:57]=1

Participants

3

Reactant 2

HCID 58292892Diethyl (4-{[4-({7-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateHCID 866976892-amino-5-bromo-4-fluoro-N-methylbenzamide2×

Product 1

HCID 86697688Diethyl (4-{[4-{[4-bromo-5-fluoro-2-(methylcarbamoyl)phenyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

Procedure

Prepared analogously to Compound 1B replacing Compound 1C with 2-amino-5-bromo-4-fluoro-N-methylbenzamide (Compound 7D, 0.327 g, 1.32 mmol) to afford the title compound as 642 mg of a white solid (88% yield). 1H NMR (DMSO-d6, 400 MHz): δ 11.94 (br. s., 1H), 9.15 (br. s., 1H), 8.88 (d, J=4.6 Hz, 1H), 8.53 (br. s., 1H), 8.42 (s, 1H), 8.08 (d, J=7.8 Hz, 1H), 7.47 (d, J=7.6 Hz, 1H), 7.02 (s, 1H), 6.82-6.90 (m, 1H), 3.93-4.02 (m, 4H), 3.77 (s, 3H), 3.18-3.27 (m, 2H), 2.77 (d, J=4.3 Hz, 3H), 1.19 (t, J=7.1 Hz, 6H). MS (ESI): m/z 664.09 [M+H]+. UPLC: tR=1.60 min (UPLC-TOF: polar—3 min).

Sources & evidence

ORD record
ord-f8bd9dd6db714d12a09a3b95154b687f
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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