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

Participants

Role	Name	HCID	Charge
Reactant	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	HCID 58292892	—
Reactant	11-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-oxide	HCID 76518268	—
Reactant	3-Amino-6-bromo-N-methoxypyridine-2-carboxamide	HCID 86697774	—
Product	Diethyl (4-{[4-{[6-bromo-2-(methoxycarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate	HCID 86697773	23%

Reaction Steps

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)

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09133224B2
Source dataset	uspto-grants-2015_09
ORD ID	ord-9a30eec100f34de99bdb0bf08fe265a2
Source note	uspto-grants-2015_09