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

HRID 2279779Notes

Reaction equation

HRID 2279779 reaction equation
C(N(CC)C(C1C=C(C2C=NN(CCCO)C=2)C=CC=1NC1C(C(F)(F)F)=CN=C(NC2C=CC(CP(=O)(O)OCC)=CC=2OC)N=1)=O)C.[F:50][C:51]1[C:52]([C:95](=[O:98])[NH:96][CH3:97])=[C:53]([NH:66][C:67]2[C:72]([C:73]([F:76])([F:75])[F:74])=[CH:71][N:70]=[C:69]([NH:77][C:78]3[CH:92]=[CH:91][C:81]([CH2:82][P:83](=[O:90])([O:87]CC)[O:84][CH2:85][CH3:86])=[CH:80][C:79]=3[O:93][CH3:94])[N:68]=2)[CH:54]=[CH:55][C:56]=1[C:57]1[CH:58]=[N:59][N:60]([CH2:62][CH2:63][CH2:64][OH:65])[CH:61]=1>>[F:50][C:51]1[C:52]([C:95](=[O:98])[NH:96][CH3:97])=[C:53]([NH:66][C:67]2[C:72]([C:73]([F:75])([F:76])[F:74])=[CH:71][N:70]=[C:69]([NH:77][C:78]3[CH:92]=[CH:91][C:81]([CH2:82][P:83](=[O:87])([OH:90])[O:84][CH2:85][CH3:86])=[CH:80][C:79]=3[O:93][CH3:94])[N:68]=2)[CH:54]=[CH:55][C:56]=1[C:57]1[CH:58]=[N:59][N:60]([CH2:62][CH2:63][CH2:64][OH:65])[CH:61]=1

Participants

3

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)phosphonateHCID 86697730Diethyl (4-{[4-({3-fluoro-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxy benzyl)phosphonate2×

Product 1

HCID 86697729Ethyl hydrogen (4-{[4-({3-fluoro-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 99%

Procedure

Prepared analogously to Compound 3A using diethyl (4-{[4-({3-fluoro-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 27B, 200 mg, 282 μmol) to afford 190 mg of the title compound (99%). 1H NMR (400 MHz, CD3OD) δ=8.31 (s, 1H), 8.20 (s, 1H), 7.93 (s, 1H), 7.86 (d, J=8.6 Hz, 1H), 7.77 (d, J=7.6 Hz, 1H), 7.67 (d, J=8.6 Hz, 1H), 7.04 (s, 1H), 6.69 (d, J=7.3 Hz, 1H), 4.37 (t, J=6.8 Hz, 2H), 3.91 (s, 3H), 3.81 (quin, J=7.0 Hz, 2H), 3.62 (t, J=6.1 Hz, 2H), 2.95 (s, 1H), 2.90 (s, 4H), 2.14 (quin, J=6.5 Hz, 2H), 1.15 (t, J=7.1 Hz, 3H). MS (ESI): m/z=682.19 [M+H]+. UPLC: tR=1.11 min (UPLC-TOF: polar—3 min).

Sources & evidence

ORD record
ord-c5f5e32a859d457fb8b0bcae1335f20b
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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