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

HRID 2279845Notes

Reaction equation

HRID 2279845 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.[NH2:50][C:51]1[C:52]([C:67]([NH:69][CH3:70])=[O:68])=[N:53][C:54]([C:57]2[C:58]([Cl:66])=[N:59][N:60]([CH2:62][CH2:63][CH2:64][OH:65])[CH:61]=2)=[CH:55][CH:56]=1>>[Cl:66][C:58]1[C:57]([C:54]2[N:53]=[C:52]([C:67](=[O:68])[NH:69][CH3:70])[C:51]([NH:50][C:26]3[C:27]([C:28]([F:29])([F:30])[F:31])=[CH:22][N:23]=[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:25]=3)=[CH:56][CH:55]=2)=[CH:61][N:60]([CH2:62][CH2:63][CH2:64][OH:65])[N:59]=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 866977833-amino-6-[3-chloro-1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-N-methylpyridine-2-carboxamide2×

Product 1

HCID 86697782diethyl (4-{[4-({6-[3-chloro-1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 59%

Procedure

Prepared analogously to Compound 1B using 3-amino-6-[3-chloro-1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-N-methylpyridine-2-carboxamide (Compound 49C, 365 mg, 1.18 mmol) to afford 480 mg of the title compound (59%). 1H NMR (400 MHz, CD3OD) δ 9.06 (br. s., 1H), 8.51 (s, 1H), 8.35 (s, 1H), 7.89 (d, J=9.1 Hz, 1H), 7.82 (d, J=8.1 Hz, 1H), 7.04 (t, J=2.0 Hz, 1H), 6.91 (td, J=2.3, 8.1 Hz, 1H), 4.26 (t, J=6.9 Hz, 2H), 4.00-4.11 (m, 4H), 3.89 (s, 3H), 3.59 (t, J=6.1 Hz, 2H), 3.35 (s, 1H), 3.23 (s, 1H), 2.98 (s, 3H), 2.11 (quin, J=6.5 Hz, 2H), 1.22-1.29 (m, 6H). MS (ESI): m/z=727.38/729.32 [M+H]+. UPLC: tR=1.35 min (UPLC-TOF: polar—2 min).

Sources & evidence

ORD record
ord-775fe5affd374302b2e3035fbf926430
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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