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-{[6-bromo-2-(methoxycarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

HRID 2279833Notes

Reaction equation

HRID 2279833 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[C:52]([C:58]([NH:60][O:61][CH3:62])=[O:59])=[N:53][C:54]([Br:57])=[CH:55][CH:56]=1.C(OP1(=O)CC2C=CC(=CC=2)NC2=NC(=C(C(F)(F)F)C=N2)NC2C=CC(=NC=2C(NC)=O)C2=CN(N=C2)CCCCO1)C>>[Br:57][C:54]1[N:53]=[C:52]([C:58](=[O:59])[NH:60][O:61][CH3:62])[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)=[CH:56][CH:55]=1

Participants

4

Reactant 3

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 7651826811-ethoxy-N-methyl-21-(trifluoromethyl)-10-oxa-4,5,17,19,23,26,29-heptaaza-11-phosphapentacyclo[22.2.2.213,16.12,5.118,22]dotriaconta-1(26),2(32),3,13,15,18(29),19,21,24,27,30-undecaene-25-carboxamide 11-oxide2×HCID 866977743-Amino-6-bromo-N-methoxypyridine-2-carboxamide2×

Product 1

HCID 86697773Diethyl (4-{[4-{[6-bromo-2-(methoxycarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 23%

Procedure

This material was prepared analogously to compound 1B using 3-Amino-6-bromo-N-methoxypyridine-2-carboxamide (Compound 46D, 302.0 mg, 1.227 mmol) and diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 1 E, 612.6 mg, 1.350 mmol) to isolate 189 mg of the title compound (23%). 1H NMR (400 MHz, DMSO-d6) δ 12.18 (s, 1H), 11.88 (s, 1H), 9.21 (br. s., 1H), 8.87 (br. s., 1H), 8.44 (s, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.38 (br. s., 1H), 7.06 (s, 1H), 6.90 (d, J=8.1 Hz, 1H), 3.96-4.05 (m, 4H), 3.74 (s, 3H), 3.70 (s, 3H), 3.29 (d, J=21.2 Hz, 2H), 1.20 (t, J=7.0 Hz, 6H)

Sources & evidence

ORD record
ord-9a30eec100f34de99bdb0bf08fe265a2
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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