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

HRID 2279725Notes

Reaction equation

HRID 2279725 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[CH:9]=[C:8]([C:10]2[CH:11]=[CH:12][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=2C[N:16]([CH3:19])[C:15]3=[O:20])[CH:7]=[N:6]1.[NH2:50]C1C(C(NC)=O)=NC(C2C=NN(CCCO)C=2)=CC=1>>[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[CH:9]=[C:8]([C:10]2[N:50]=[C:14]([C:15](=[O:20])[NH:16][CH3:19])[C:13]([NH:21][C:22]3[C:27]([C:28]([F:29])([F:31])[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:12][CH:11]=2)[CH:7]=[N:6]1

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 678187943-amino-6-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-N-methylpyridine-2-carboxamide2×

Product 1

HCID 86697685Diethyl (4-{[4-({6-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 68%

Procedure

Prepared analogously to Compound 1B replacing Compound 1C with 3-amino-6-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-N-methylpyridine-2-carboxamide (Compound 6C, 220.0 mg, 0.7991 mmol) to afford 337 mg of the title compound (68%). 1H NMR (400 MHz, CDCl3) δ 12.19 (s, 1H), 9.04 (d, J=9.1 Hz, 1H), 8.36-8.44 (m, 2H), 8.21 (s, 1H), 8.08 (s, 1H), 8.04 (br. s., 1H), 7.63 (d, J=8.8 Hz, 1H), 7.52 (s, 1H), 6.95 (td, J=2.3, 8 Hz, 1H), 6.86 (t, J=1.9 Hz, 1H), 4.40 (t, J=6.2 Hz, 2H), 3.97-4.11 (m, 4H), 3.91 (s, 3H), 3.65 (q, J=5.3 Hz, 2H), 3.18 (d, J=21.1 Hz, 2H), 3.09 (d, J=5.1 Hz, 3H), 2.11 (quin, J=5.9 Hz, 2H), 1.26 (t, J=7.1 Hz, 6H) [OH proton obscured]. MS (ES+): m/z 693.75 [M+H]+. UPLC: tR=1.24 min (UPLC-SQD: analytical—2 min).

Sources & evidence

ORD record
ord-5683cb7ece524f14a9d1770dac344a48
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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