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-({6-[1-(3-hydroxypropyl)-5-methyl-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl) pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

HRID 2279810Notes

Reaction equation

HRID 2279810 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.[OH:50][CH2:51][CH2:52][CH2:53][N:54]1[C:58]([CH3:59])=[C:57]([C:60]2[N:65]=[C:64]([C:66](=[O:69])[NH:67][CH3:68])[C:63]([NH:70][C:71]3[C:76]([C:77]([F:80])([F:79])[F:78])=[CH:75][N:74]=[C:73]([NH:81][C:82]4[CH:96]=[CH:95][C:85]([CH2:86][P:87](=[O:94])([O:91]CC)[O:88][CH2:89][CH3:90])=[CH:84][C:83]=4[O:97][CH3:98])[N:72]=3)=[CH:62][CH:61]=2)[CH:56]=[N:55]1>>[OH:50][CH2:51][CH2:52][CH2:53][N:54]1[C:58]([CH3:59])=[C:57]([C:60]2[N:65]=[C:64]([C:66](=[O:69])[NH:67][CH3:68])[C:63]([NH:70][C:71]3[C:76]([C:77]([F:80])([F:78])[F:79])=[CH:75][N:74]=[C:73]([NH:81][C:82]4[CH:96]=[CH:95][C:85]([CH2:86][P:87](=[O:91])([OH:94])[O:88][CH2:89][CH3:90])=[CH:84][C:83]=4[O:97][CH3:98])[N:72]=3)=[CH:62][CH:61]=2)[CH:56]=[N:55]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 86697752Diethyl (4-{[4-({6-[1-(3-hydroxypropyl)-5-methyl-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate2×

Product 1

HCID 86697751Ethyl hydrogen (4-{[4-({6-[1-(3-hydroxypropyl)-5-methyl-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl) pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 107.2%

Procedure

Prepared analogously to Compound 3A using diethyl (4-{[4-({6-[1-(3-hydroxypropyl)-5-methyl-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl) pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 35B, 270 mg, 382 μmol) to afford 278 mg of the title compound (100%). 1H NMR (400 MHz, CD3OD) δ 8.95-9.04 (m, 1H), 8.26 (s, 1H), 7.96-8.01 (m, 1H), 7.71-7.80 (m, 1H), 7.51 (d, J=9.1 Hz, 1H), 7.08 (s, 1H), 6.83-6.90 (m, 1H), 4.25 (t, J=7.1 Hz, 2H), 3.81-3.92 (m, 5H), 3.55-3.60 (m, 2H), 2.97 (d, J=21.0 Hz, 2H), 2.92 (s, 1H), 2.61 (s, 3H), 2.03 (t, J=6.7 Hz, 2H), 1.17 (t, J=7.1 Hz, 3H). MS (ESI): m/z=679.67 [M+H]+. UPLC: tR=1.15 min (UPLC-SQD: analytical—2 min).

Sources & evidence

ORD record
ord-9a216ad9c7934c519ae278965919ca39
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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