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

HRID 2279744Notes

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[CH:65]=[CH:64][C:63]([NH:66][C:67]3[C:72]([C:73]([F:76])([F:75])[F:74])=[CH:71][N:70]=[C:69]([NH:77][C:78]4[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]=4[O:93][CH3:94])[N:68]=3)=[C:62]([C:95](=[O:98])[NH:96][CH3:97])[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[CH:65]=[CH:64][C:63]([NH:66][C:67]3[C:72]([C:73]([F:74])([F:75])[F:76])=[CH:71][N:70]=[C:69]([NH:77][C:78]4[CH:92]=[CH:91][C:81]([CH2:82][P:83](=[O:87])([OH:90])[O:84][CH2:85][CH3:86])=[CH:80][C:79]=4[O:93][CH3:94])[N:68]=3)=[C:62]([C:95](=[O:98])[NH:96][CH3:97])[CH:61]=2)[CH:57]=[N:56]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 86697700diethyl (4-{[4-({4-[1-(4-hydroxybutyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate2×

Product 1

HCID 86697699Ethyl hydrogen (4-{[4-({4-[1-(4-hydroxybutyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 96.7%

Procedure

Prepared analogously to Compound 3A using diethyl (4-{[4-({4-[1-(4-hydroxybutyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 14B, 63.6 mg, 0.09 mmol) to afford 59 mg of the title compound (96%). 1H NMR (400 MHz, CD3OD) δ 8.34 (d, J=8.6 Hz, 1H), 8.28 (s, 1H), 8.15 (s, 1H), 7.91 (d, J=0.5 Hz, 1H), 7.87 (d, J=8.1 Hz, 1H), 7.83 (d, J=2.3 Hz, 1H), 7.65 (dd, J=2.15, 8.72 Hz, 1H), 7.06 (t, J=1.9 Hz, 1H), 6.80 (dd, J=1.9, 8.2 Hz, 1H), 4.23 (t, J=6.9 Hz, 2H), 3.90 (s, 3H), 3.83 (quin, J=7.0 Hz, 2H), 3.56-3.62 (m, 2H), 2.93-3.00 (m, 2H), 2.91 (s, 3H), 1.92-2.02 (m, 2H), 1.50-1.60 (m, 2H), 1.14 (t, J=7.1 Hz, 3H). MS (ESI): m/z 678.79 [M+H]+. UPLC: tR=1.02 min (UPLC-SQD: analytical—2 min).

Sources & evidence

ORD record: ord-714f6d32501849d79e76fcc65b2af483
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133224B2

Reaction notes

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