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-(4-hydroxybutyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

HRID 2279747Notes

Reaction equation

HRID 2279747 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][CH2:54][N:55]1[CH:59]=[C:58]([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:57]=[N:56]1>>[OH:50][CH2:51][CH2:52][CH2:53][CH2:54][N:55]1[CH:59]=[C:58]([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:57]=[N:56]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 86697702diethyl (4-{[4-({6-[1-(4-hydroxybutyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate2×

Product 1

HCID 86697701Ethyl hydrogen (4-{[4-({6-[1-(4-hydroxybutyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 103.2%

Procedure

Prepared analogously to Compound 3A using diethyl (4-{[4-({6-[1-(4-hydroxybutyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 15B, 95 mg, 0.13 mmol) to afford 91 mg of the title compound (99%). 1H NMR (400 MHz, CD3OD) δ 8.96 (d, J=6.1 Hz, 1H), 8.50 (s, 1H), 8.29 (s, 1H), 8.20 (s, 1H), 7.69 (d, J=9.1 Hz, 2H), 7.10 (s, 1H), 6.93 (dd, J=2.0, 8.1 Hz, 1H), 4.24 (t, J=6.9 Hz, 2H), 3.83-3.91 (m, 5H), 3.60 (t, J=6.4 Hz, 2H), 2.99-3.06 (m, 2H), 2.98 (s, 3H), 1.94-2.04 (m, 2H), 1.51-1.61 (m, 2H), 1.16 (t, J=7.1 Hz, 3H). MS (ESI): m/z 679.80 [M+H]+. UPLC: tR=1.11 min (UPLC-SQD: analytical—2 min).

Sources & evidence

ORD record
ord-b6808a7c041f42bc9120c6027bf88f41
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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