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-[5-cyano-1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

HRID 2279858Notes

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.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.[NH2:94][C:95]1[C:96]([C:112]([NH:114][CH3:115])=[O:113])=[N:97][C:98]([C:101]2[CH:102]=[N:103][N:104]([CH2:108][CH2:109][CH2:110][OH:111])[C:105]=2[C:106]#[N:107])=[CH:99][CH:100]=1>>[C:106]([C:105]1[N:104]([CH2:108][CH2:109][CH2:110][OH:111])[N:103]=[CH:102][C:101]=1[C:98]1[N:97]=[C:96]([C:112](=[O:113])[NH:114][CH3:115])[C:95]([NH:94][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:100][CH:99]=1)#[N:107]

Participants

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)phosphonate

HCID 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 866977963-amino-6-[5-cyano-1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-N-methylpyridine-2-carboxamide2×

Product 1

HCID 86697795diethyl (4-{[4-({6-[5-cyano-1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 55%

Procedure

Prepared analogously to Compound 1B using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 1 E, 218 mg, 0.480 mmol) and 3-amino-6-[5-cyano-1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-N-methylpyridine-2-carboxamide (Compound 53C, 151 mg, 0.504 mmol) to afford 191 mg of the title compound (55%). 1H NMR (400 MHz, CD3OD) δ 9.19 (br. s., 1H), 8.47 (s, 1H), 8.38 (s, 1H), 7.91 (d, J=8.8 Hz, 1H), 7.69 (br. s., 1H), 7.08 (s, 1H), 6.98 (d, J=7.8 Hz, 1H), 4.52 (t, J=6.9 Hz, 2H), 4.01-4.14 (m, 3H), 3.88 (s, 2H), 3.61 (t, J=6.1 Hz, 2H), 3.36 (s, 2H), 2.99 (s, 3H), 2.17 (quin, J=6.5 Hz, 2H), 1.18-1.31 (m, 8H). MS (ESI): m/z=718.56 [M+H]+. UPLC: tR=1.36 min (UPLC-TOF: polar—2 min).

Sources & evidence

ORD record: ord-854fbe495a594e7286d25747b5246df0
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133224B2

Reaction notes

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