Ethyl hydrogen (4-{[4-({2-(diethylcarbamoyl)-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate → Ethyl hydrogen (4-{[4-({2-(dimethylcarbamoyl)-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

HRID 2279743Notes

Reaction equation

[CH2:1]([N:3]([CH2:48]C)[C:4]([C:6]1[CH:11]=[C:10]([C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH2:18][CH2:19][OH:20])[CH:16]=2)[CH:9]=[CH:8][C:7]=1[NH:21][C:22]1[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][N:25]=[C:24]([NH:32][C:33]2[CH:45]=[CH:44][C:36]([CH2:37][P:38](=[O:43])([OH:42])[O:39][CH2:40][CH3:41])=[CH:35][C:34]=2[O:46][CH3:47])[N:23]=1)=[O:5])C.CN(C)C(C1C=C(C2C=NN(CCCO)C=2)C=CC=1NC1C(C(F)(F)F)=CN=C(NC2C=CC(CP(=O)(OCC)OCC)=CC=2OC)N=1)=O>>[CH3:48][N:3]([CH3:1])[C:4]([C:6]1[CH:11]=[C:10]([C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH2:18][CH2:19][OH:20])[CH:16]=2)[CH:9]=[CH:8][C:7]=1[NH:21][C:22]1[C:27]([C:28]([F:29])([F:30])[F:31])=[CH:26][N:25]=[C:24]([NH:32][C:33]2[CH:45]=[CH:44][C:36]([CH2:37][P:38](=[O:42])([OH:43])[O:39][CH2:40][CH3:41])=[CH:35][C:34]=2[O:46][CH3:47])[N:23]=1)=[O:5]

Participants

Reactant 2

HCID 86697678Ethyl hydrogen (4-{[4-({2-(diethylcarbamoyl)-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

HCID 86697698diethyl (4-{[4-({2-(dimethylcarbamoyl)-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate2×

Product 1

HCID 86697697Ethyl hydrogen (4-{[4-({2-(dimethylcarbamoyl)-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 56%

Procedure

Prepared analogously to Compound 3A using diethyl (4-{[4-({2-(dimethylcarbamoyl)-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 12B, 72 mg, 102 μmol) to afford 39 mg of the title compound (56%). 1H NMR (400 MHz, CD3OD) δ 8.26 (s, 1H), 8.18 (s, 1H), 7.93 (s, 1H), 7.79-7.86 (m, 1H), 7.70-7.79 (m, 2H), 7.59 (d, J=2.0 Hz, 1H), 7.01 (s, 1H), 6.61 (br. s., 1H), 4.32 (t, J=6.8 Hz, 2H), 3.88 (s, 3H), 3.76 (quin, J=6.9 Hz, 2H), 3.59 (t, J=6.1 Hz, 2H), 3.04 (s, 3H), 2.90 (d, J=3.8 Hz, 4H), 2.85 (s, 1H), 2.04-2.17 (m, 2H), 1.11 (t, J=7.1 Hz, 3H). MS (ESI): m/z 678.70 [M+H]+. UPLC: tR=0.95 min (UPLC-SQD: analytical—2 min).

Sources & evidence

ORD record: ord-efc7ba461d00446db5fee3e7b51ebc21
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133224B2

Reaction notes

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