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

HRID 2279844Notes

Reaction equation

HRID 2279844 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.[Cl:50][C:51]1[C:55]([C:56]2[N:61]=[C:60]([C:62](=[O:65])[NH:63][CH3:64])[C:59]([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)=[CH:58][CH:57]=2)=[CH:54][N:53]([CH2:95][CH2:96][CH2:97][OH:98])[N:52]=1>>[Cl:50][C:51]1[C:55]([C:56]2[N:61]=[C:60]([C:62](=[O:65])[NH:63][CH3:64])[C:59]([NH:66][C:67]3[C:72]([C:73]([F:75])([F:74])[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)=[CH:58][CH:57]=2)=[CH:54][N:53]([CH2:95][CH2:96][CH2:97][OH:98])[N:52]=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 86697782diethyl (4-{[4-({6-[3-chloro-1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate2×

Product 1

HCID 86697781Ethyl hydrogen (4-{[4-({6-[3-chloro-1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 96.3%

Procedure

Prepared analogously to Compound 3A using diethyl (4-{[4-({6-[3-chloro-1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 49B, 480 mg, 0.661 mmol) to afford 445 mg of the desired product (96%). 1H NMR (400 MHz, CD3OD) δ 8.93-9.09 (m, 1H), 8.59 (s, 1H), 8.32 (s, 1H), 7.88 (d, J=9.1 Hz, 1H), 7.62 (d, J=6.6 Hz, 1H), 7.12 (s, 1H), 6.93 (d, J=8.1 Hz, 1H), 4.27 (t, J=6.8 Hz, 2H), 3.82-3.92 (m, 5H), 3.60 (t, J=6.1 Hz, 2H), 3.05 (s, 1H), 2.97-3.02 (m, 4H), 2.11 (quin, J=6.4 Hz, 2H), 1.16 (t, J=6.9 Hz, 3H). MS (ESI): m/z=699.54/701.48 [M+H]+. UPLC: tR=1.21 min (UPLC-TOF: polar—2 min).

Sources & evidence

ORD record
ord-16eddf8c2e994582950afc8fad360793
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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