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

HRID 2279848Notes

Reaction equation

HRID 2279848 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=C[N:59](N=C2)CCCCO1)C.[NH2:94][C:95]1[CH:104]=[CH:103][C:102]([C:105]2[CH:106]=[N:107][N:108]([C:110]([CH3:115])([CH2:112][CH2:113][OH:114])[CH3:111])[CH:109]=2)=C[C:96]=1[C:97]([NH:99][CH3:100])=[O:98]>>[OH:114][CH2:113][CH2:112][C:110]([N:108]1[CH:109]=[C:105]([C:102]2[N:59]=[C:96]([C:97](=[O:98])[NH:99][CH3:100])[C:95]([NH:94][C:22]3[C:27]([C:28]([F:31])([F:29])[F:30])=[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)=[CH:104][CH:103]=2)[CH:106]=[N:107]1)([CH3:111])[CH3:115]

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 866977862-amino-5-[1-(4-hydroxy-2-methylbutan-2-yl)-1H-pyrazol-4-yl]-N-methylbenzamide2×

Product 1

HCID 86697785diethyl (4-{[4-({6-[1-(4-hydroxy-2-methylbutan-2-yl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 24%

Procedure

Prepared analogously to Compound 1B using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 1 E, 304 mg, 0.671 mmol) and 2-amino-5-[1-(4-hydroxy-2-methylbutan-2-yl)-1H-pyrazol-4-yl]-N-methylbenzamide (Compound 50C, 213.1 mg, 0.705 mmol) to afford 117 mg of the title compound (24%). 1H NMR (400 MHz, CD3OD) δ 9.01 (d, J=8.8 Hz, 1H), 8.62 (s, 1H), 8.34 (s, 1H), 8.27 (s, 1H), 7.70-7.76 (m, 2H), 7.07 (s, 1H), 6.96 (dd, J=2.3, 10.6 Hz, 1H), 4.01-4.12 (m, 5H), 3.88 (s, 3H), 3.42 (t, J=7.1 Hz, 2H), 2.99 (s, 3H), 2.14-2.24 (m, 3H), 1.70 (s, 6H), 1.21-1.30 (m, 6H). MS (ESI): m/z=721.49 [M+H]+. UPLC: tR=1.33 min (UPLC-TOF: polar—2 min).

Sources & evidence

ORD record
ord-01d79de1de594c10bb168dee7f774e6c
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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