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 → {4-[4-(6-Bromo-2-methylcarbamoyl-pyridin-3-ylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-3-methoxy-benzyl}-phosphonic acid diethyl ester

HRID 2279824Notes

Reaction equation

HRID 2279824 reaction equation
OCCCN1C=C(C2C=C[C:13]([NH:21][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)=[C:14]3C=2[CH2:17][N:16](C)[C:15]3=[O:20])C=N1.NC1C(C(NC)=O)=[N:53][C:54]([Br:57])=[CH:55][CH:56]=1>>[CH2:43]([O:42][P:38]([CH2:37][C:36]1[CH:46]=[CH:47][C:33]([NH:32][C:24]2[N:23]=[C:22]([NH:21][C:13]3[C:14]([C:15](=[O:20])[NH:16][CH3:17])=[N:53][C:54]([Br:57])=[CH:55][CH:56]=3)[C:27]([C:28]([F:30])([F:29])[F:31])=[CH:26][N:25]=2)=[C:34]([O:48][CH3:49])[CH:35]=1)(=[O:45])[O:39][CH2:40][CH3:41])[CH3:44]

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 866976863-Amino-6-bromo-N-methylpicolinamide2×

Product 1

HCID 86697764{4-[4-(6-Bromo-2-methylcarbamoyl-pyridin-3-ylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-3-methoxy-benzyl}-phosphonic acid diethyl esterYield 78%

Procedure

Prepared analogously to Compound 1B replacing Compound 10 with 3-amino-6-bromo-N-methylpyridine-2-carboxamide (Compound 6D, 279 mg, 1.21 mmol). The reaction mixture was concentrated in vacuo and purified using a Teledyne ISCO Combiflash® Rf system [0→5% MeOH in DCM] to afford 661 mg of the title compound (78%). 1H NMR (400 MHz, CD3OD) δ 8.94-9.11 (m, 1H), 8.37 (s, 1H), 7.68 (d, J=7.1 Hz, 1H), 7.58 (d, J=9.1 Hz, 1H), 7.07 (t, J=2.0 Hz, 1H), 6.94 (td, J=2.4, 8.2 Hz, 1H), 4.04-4.16 (m, 4H), 3.88 (s, 3H), 3.33-3.34 (m, 1H), 3.28 (s, 1H), 2.94 (s, 3H), 1.29 (t, J=7.1 Hz, 6H). MS (ESI): m/z 647.53/649.53 [M+H]+. UPLC: tR=1.49 min (UPLC-TOF: polar—2 min).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. custompurified

Sources & evidence

ORD record
ord-d38d675f0c9f454cb59438c18f32338e
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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