2-amino-N,N-diethyl-5-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]benzamide → Ethyl hydrogen (4-{[4-({6-[1-(2,2-difluoro-3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

HRID 2279878Notes

Reaction equation

HRID 2279878 reaction equation
NC1C=CC(C2C=NN(CCCO)C=2)=CC=1C(N(CC)CC)=O.[F:24][C:25]([F:73])([CH2:71][OH:72])[CH2:26][N:27]1[CH:31]=[C:30]([C:32]2[N:37]=[C:36]([C:38](=[O:41])[NH:39][CH3:40])[C:35]([NH:42][C:43]3[C:48]([C:49]([F:52])([F:51])[F:50])=[CH:47][N:46]=[C:45]([NH:53][C:54]4[CH:68]=[CH:67][C:57]([CH2:58][P:59](=[O:66])([O:63]CC)[O:60][CH2:61][CH3:62])=[CH:56][C:55]=4[O:69][CH3:70])[N:44]=3)=[CH:34][CH:33]=2)[CH:29]=[N:28]1>>[F:73][C:25]([F:24])([CH2:71][OH:72])[CH2:26][N:27]1[CH:31]=[C:30]([C:32]2[N:37]=[C:36]([C:38](=[O:41])[NH:39][CH3:40])[C:35]([NH:42][C:43]3[C:48]([C:49]([F:52])([F:51])[F:50])=[CH:47][N:46]=[C:45]([NH:53][C:54]4[CH:68]=[CH:67][C:57]([CH2:58][P:59](=[O:63])([OH:66])[O:60][CH2:61][CH3:62])=[CH:56][C:55]=4[O:69][CH3:70])[N:44]=3)=[CH:34][CH:33]=2)[CH:29]=[N:28]1

Participants

3

Reactant 2

HCID 866976802-amino-N,N-diethyl-5-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]benzamideHCID 86697817diethyl (4-{[4-({6-[1-(2,2-difluoro-3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate2×

Product 1

HCID 86697816Ethyl hydrogen (4-{[4-({6-[1-(2,2-difluoro-3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 93.4%

Procedure

Prepared analogously to Compound 3C using diethyl (4-{[4-({6-[1-(2,2-difluoro-3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 59B, 388 mg, 0.532 mmol) to afford 348 mg of the title compound (93%). 1H NMR (400 MHz, CD3OD) δ 8.96-9.11 (m, 2H), 8.56 (s, 1H), 8.31 (s, 2H), 7.74 (d, J=9.1 Hz, 1H), 7.10 (s, 1H), 6.94 (d, J=8.1 Hz, 1H), 4.66 (d, J=7.6 Hz, 2H), 3.88 (quin, J=6.9 Hz, 5H), 3.65-3.77 (m, 2H), 3.06 (s, 5H), 1.15 (t, J=6.9 Hz, 3H). MS (ESI): m/z=701.68 [M+H]+. UPLC: tR=1.27 min (UPLC-TOF: polar—2 min).

Sources & evidence

ORD record
ord-33c4d323e52948f39aa2b9502ce94c17
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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