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-[(7-{1-[(2S)-2,3-dihydroxypropyl]-1H-pyrazol-4-yl}-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)-3-methoxy benzyl]phosphonate

HRID 2279720Notes

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]3[C:18]=2[CH2:17][N:16]([CH3:19])[C:15]3=[O:20])[CH:7]=[N:6]1.NC1C=CC(C2C=NN(C[C@H]3COC(C)(C)O3)C=2)=C2C=1C(=[O:60])N(C)C2>>[CH2:40]([O:39][P:38]([CH2:37][C:36]1[CH:46]=[CH:47][C:33]([NH:32][C:24]2[N:23]=[C:22]([NH:21][C:13]3[CH:12]=[CH:11][C:10]([C:8]4[CH:7]=[N:6][N:5]([CH2:4][C@H:3]([OH:60])[CH2:2][OH:1])[CH:9]=4)=[C:18]4[C:14]=3[C:15](=[O:20])[N:16]([CH3:19])[CH2:17]4)[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][N:25]=2)=[C:34]([O:48][CH3:49])[CH:35]=1)(=[O:45])[O:42][CH2:43][CH3:44])[CH3:41]

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 678116527-amino-4-(1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-1H-pyrazol-4-yl)-2-methyl-2,3-dihydro-1H-isoindol-1-one2×

Product 1

HCID 49821942Diethyl[4-({4-[(7-{1-[(2S)-2,3-dihydroxypropyl]-1H-pyrazol-4-yl}-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)-3-methoxy benzyl]phosphonateYield 48%

Procedure

Prepared analogously to Compound 1B replacing Compound 1C with 7-amino-4-(1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-1H-pyrazol-4-yl)-2-methyl-2,3-dihydro-1H-isoindol-1-one (Compound 5C, 337 mg, 742 μmol) to afford 254 mg of the desired product (48%). 1H NMR (400 MHz, CD3OD) δ 8.49 (br. s., 1H), 8.34 (s, 1H), 8.09 (s, 1H), 7.96 (s, 1H), 7.67-7.77 (m, 2H), 7.11 (s, 1H), 7.00 (d, J=8.1 Hz, 1H), 4.61 (s, 2H), 4.37 (dd, J=4.3, 13.9 Hz, 1H), 4.15-4.24 (m, 1H), 4.00-4.14 (m, 5H), 3.90 (s, 3H), 3.52-3.56 (m, 2H), 3.35 (d, J=7.1 Hz, 2H), 3.21 (s, 3H), 1.26 (dt, J=2.7, 7 Hz, 6H). MS (ESI): m/z 720.23 [M+H]+. UPLC: tR=1.12 min (UPLC-TOF: polar—3 min).

Sources & evidence

ORD record: ord-7fcbf88021704ea9a934ccff4b6d113e
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133224B2

Reaction notes

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