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-({7-[1-(4-hydroxybutyl)-1H-pyrazol-4-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

HRID 2279752Notes

Reaction equation

HRID 2279752 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:61]=[CH:62][C:63]([NH:71][C:72]3[C:77]([C:78]([F:81])([F:80])[F:79])=[CH:76][N:75]=[C:74]([NH:82][C:83]4[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]=4[O:98][CH3:99])[N:73]=3)=[C:64]3[C:68]=2[CH2:67][N:66]([CH3:69])[C:65]3=[O:70])[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:61]=[CH:62][C:63]([NH:71][C:72]3[C:77]([C:78]([F:81])([F:80])[F:79])=[CH:76][N:75]=[C:74]([NH:82][C:83]4[CH:97]=[CH:96][C:86]([CH2:87][P:88](=[O:92])([OH:95])[O:89][CH2:90][CH3:91])=[CH:85][C:84]=4[O:98][CH3:99])[N:73]=3)=[C:64]3[C:68]=2[CH2:67][N:66]([CH3:69])[C:65]3=[O:70])[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 86697709diethyl (4-{[4-({7-[1-(4-hydroxybutyl)-1H-pyrazol-4-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate2×

Product 1

HCID 86697708Ethyl hydrogen (4-{[4-({7-[1-(4-hydroxybutyl)-1H-pyrazol-4-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 101.9%

Procedure

Prepared analogously to Compound 3A using diethyl (4-{[4-({7-[1-(4-hydroxybutyl)-1H-pyrazol-4-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 17B, 73 mg, 101 μmol) to afford 71 mg of the title compound (100%). 1H NMR (400 MHz, CD3OD) δ 8.49 (d, J=6.57 Hz, 1H), 8.23 (s, 1H), 8.04 (br. s., 1H), 7.77 (s, 2H), 7.57 (d, J=8.84 Hz, 1H), 7.11 (s, 1H), 6.95 (d, J=8.08 Hz, 1H), 4.42 (s, 2H), 4.22 (t, J=7.07 Hz, 2H), 3.82-3.92 (m, 5H), 3.59 (t, J=6.44 Hz, 2H), 3.07-3.11 (m, 3H), 3.03 (d, J=21, 2H), 1.97 (quin, J=7.33 Hz, 2H), 1.51-1.60 (m, 2H), 1.17 (t, J=7.07 Hz, 3H). MS (ESI): m/z 690.80 [M+H]+. UPLC: tR=1.07 min (UPLC-SQD: analytical—2 min).

Sources & evidence

ORD record
ord-cc61fb020b154bb18cd310e513f7ba83
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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