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-({4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

HRID 2279733Notes

Reaction equation

HRID 2279733 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]=4OC)[N:23]=3)=[C:14]3[C:18]=2[CH2:17][N:16](C)[C:15]3=[O:20])[CH:7]=[N:6]1.ClC1C(C(F)(F)F)=CN=C(NC2C=CC(CP(=O)(OCC)OCC)=CC=2)N=1.NC1C=CC(C2C=NN(CCCO)C=2)=CC=1C(NC)=O>>[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: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][CH:34]=4)[N:23]=3)=[C:14]([C:15](=[O:20])[NH:16][CH3:17])[CH:18]=2)[CH:7]=[N:6]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 678140542-amino-5-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-N-methylbenzamide2×HCID 86654003Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

Product 1

HCID 86697690Diethyl (4-{[4-({4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonateYield 68%

Procedure

Prepared analogously to Compound 1B replacing Compound 1E with Compound 2C and replacing Compound 1C with 2-amino-5-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-N-methylbenzamide (Compound 8C, 517 mg, 1.22 mmol) to afford 550 mg of the title compound (68%). 1H NMR (400 MHz, CD3OD) δ 8.36 (br. s., 1H), 8.32 (s, 1H), 8.18 (s, 1H), 8.00 (s, 1H), 7.91 (d, J=2.0 Hz, 1H), 7.69 (dd, J=2.0, 8.8 Hz, 1H), 7.47 (d, J=8.1 Hz, 2H), 7.35 (dd, J=2.4, 8.5 Hz, 2H), 4.31 (t, J=6.9 Hz, 2H), 3.98-4.10 (m, 4H), 3.57 (t, J=6.1 Hz, 2H), 3.26 (s, 2H), 2.92 (s, 3H), 2.10 (t, J=6.4 Hz, 2H), 1.23 (t, J=7.1 Hz, 6H). MS (ESI): m/z: 662.74 [M+H]+. UPLC: tR=1.11 min (UPLC-SQD: analytical—2 min).

Sources & evidence

ORD record
ord-1bdaa953c368422583aa9b62666401f3
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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