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

HRID 2279857Notes

Reaction equation

HRID 2279857 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.[C:50]([C:52]1[N:56]([CH2:57][CH2:58][CH2:59][OH:60])[N:55]=[CH:54][C:53]=1[C:61]1[N:66]=[C:65]([C:67](=[O:70])[NH:68][CH3:69])[C:64]([NH:71][C:72]2[C:77]([C:78]([F:81])([F:80])[F:79])=[CH:76][N:75]=[C:74]([NH:82][C:83]3[CH:97]=[CH:96][C:86]([CH2:87][P:88](=[O:95])([O:92]CC)[O:89][CH2:90][CH3:91])=[CH:85][C:84]=3[O:98][CH3:99])[N:73]=2)=[CH:63][CH:62]=1)#[N:51]>>[C:50]([C:52]1[N:56]([CH2:57][CH2:58][CH2:59][OH:60])[N:55]=[CH:54][C:53]=1[C:61]1[N:66]=[C:65]([C:67](=[O:70])[NH:68][CH3:69])[C:64]([NH:71][C:72]2[C:77]([C:78]([F:79])([F:81])[F:80])=[CH:76][N:75]=[C:74]([NH:82][C:83]3[CH:97]=[CH:96][C:86]([CH2:87][P:88](=[O:92])([OH:95])[O:89][CH2:90][CH3:91])=[CH:85][C:84]=3[O:98][CH3:99])[N:73]=2)=[CH:63][CH:62]=1)#[N:51]

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 86697795diethyl (4-{[4-({6-[5-cyano-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 86697794ethyl hydrogen (4-{[4-({6-[5-cyano-1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 80%

Procedure

Prepared analogously to Compound 3A using diethyl (4-{[4-({6-[5-cyano-1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 53B, 191 mg, 0.266 mmol) to afford 146 mg of the title compound (80%). 1H NMR (400 MHz, CD3OD) δ 9.15 (br. s., 1H), 8.47 (br. s., 1H), 8.33 (s, 1H), 7.89 (d, J=9.1 Hz, 1H), 7.61 (br. s., 1H), 7.12 (s, 1H), 6.95 (d, J=8.1 Hz, 1H), 4.49 (t, J=7.1 Hz, 2H), 3.83-3.93 (m, 5H), 3.60 (t, J=6.2 Hz, 2H), 2.99-3.07 (m, 2H), 2.97 (s, 3H), 2.16 (quin, J=6.5 Hz, 2H), 1.16 (t, J=7.1 Hz, 3H). MS (ESI): m/z=690.62 [M+H]+. UPLC: tR=1.26 min (UPLC-TOF: polar—2 min).

Sources & evidence

ORD record
ord-8acf0e462f794a7c88f6cf9fe1c12fec
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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