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

HRID 2279811Notes

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[CH:58]=[N:59][N:60]([CH2:63][CH2:64][CH2:65][OH:66])[C:61]=2[CH3:62])=[CH:55][CH:56]=1>>[OH:66][CH2:65][CH2:64][CH2:63][N:60]1[C:61]([CH3:62])=[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:58]=[N:59]1

Participants

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)phosphonate

HCID 67819081HCID 67819081, compound2×

Product 1

HCID 86697752Diethyl (4-{[4-({6-[1-(3-hydroxypropyl)-5-methyl-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 replacing Compound 1C with 3-Amino-6-[1-(3-hydroxypropyl)-5-methyl-1H-pyrazol-4-yl]-N-methylpyridine-2-carboxamide (Compound 35C, 177 mg, 644 μmol) to afford 270 mg of the title compound (59%). 1H NMR (400 MHz, CD3OD) d 8.59-8.68 (m, 1H), 8.30 (s, 1H), 8.03 (s, 1H), 7.76-7.86 (m, 1H), 7.58 (d, J=9.1 Hz, 1H), 7.01 (s, 1H), 6.88 (d, J=8.1 Hz, 1H), 4.26 (t, J=7.1 Hz, 2H), 4.05 (quin, J=7.3 Hz, 4H), 3.88 (s, 3H), 3.53-3.60 (m, 2H), 3.25 (d, J=21.0 Hz, 2H), 2.92-2.98 (m, 3H), 2.63 (s, 3H), 2.04 (t, J=6.7 Hz, 2H), 1.25 (t, J=7.1 Hz, 6H). MS (ESI): m/z=677.21 [M+H]+. UPLC: tR=3.8 min (ZQ3: polar—5 min).

Sources & evidence

ORD record: ord-4ee144e7d4ae4c3188c28a67f9b714ae
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133224B2

Reaction notes

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