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

HRID 2279715Notes

Reaction equation

[CH2:1]([N:3](CC)[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.OCCCN1C=C(C2C=CC(NC3C(C(F)(F)F)=CN=C(NC4C=CC(CP(=O)(OCC)OCC)=CC=4OC)N=3)=C(C(=O)NC)C=2)C=N1>>[OH:20][CH2:19][CH2:18][CH2:17][N:15]1[CH:16]=[C:12]([C:10]2[CH:9]=[CH:8][C:7]([NH:21][C:22]3[C:27]([C:28]([F:29])([F:30])[F:31])=[CH:26][N:25]=[C:24]([NH:32][C:33]4[CH:45]=[CH:44][C:36]([CH2:37][P:38](=[O:42])([OH:43])[O:39][CH2:40][CH3:41])=[CH:35][C:34]=4[O:46][CH3:47])[N:23]=3)=[C:6]([C:4](=[O:5])[NH:3][CH3:1])[CH:11]=2)[CH:13]=[N:14]1

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 86697683Diethyl (4-{[4-({4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)-phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)-phosphonate

Product 1

HCID 86697682Ethyl hydrogen (4-{[4-({4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 70%

Procedure

Prepared analogously to Compound 3A with diethyl (4-{[4-({4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (234 mg, 338 μmol) to yield 156 mg of the desired product (70%). 1H NMR (400 MHz, CD3OD) δ 8.30-8.36 (m, 1H), 8.26 (s, 1H), 8.14 (s, 1H), 7.92 (s, 1H), 7.86 (d, J=8.08 Hz, 1H), 7.83 (d, J=2.02 Hz, 1H), 7.63 (dd, J=2.02, 8.59 Hz, 1H), 7.04 (s, 1H), 6.80 (s, 1H), 4.30 (t, J=6.82 Hz, 2H), 3.88 (s, 3H), 3.84 (t, J=6.95 Hz, 2H), 3.58 (t, J=6.19 Hz, 2H), 2.92-3.02 (d, J=21.9 Hz, 2H), 2.91 (s, 3H), 2.10 (t, J=6.44 Hz, 2H), 1.15 (t, J=6.95 Hz, 3H). MS (ESI): m/z 664.21 [M+H]+. UPLC: tR=1.13 min (UPLC-TOF: polar—3 min).

Sources & evidence

ORD record: ord-d18211f8a42c4372a5bbf11ce86a418c
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133224B2

Reaction notes

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