Diethyl[4-({4-[(7-{1-[(2S)-2,3-dihydroxypropyl]-1H-pyrazol-4-yl}-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)-3-methoxy benzyl]phosphonate → Ethyl hydrogen [4-({4-[(7-{1-[(2S)-2,3-dihydroxypropyl]-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 2279719Notes

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.[CH2:50]([O:52][P:53]([CH2:58][C:59]1[CH:64]=[CH:63][C:62]([NH:65][C:66]2[N:71]=[C:70]([NH:72][C:73]3[CH:81]=[CH:80][C:79]([C:82]4[CH:83]=[N:84][N:85]([CH2:87][C@H:88]([OH:91])[CH2:89][OH:90])[CH:86]=4)=[C:78]4[C:74]=3[C:75](=[O:93])[N:76]([CH3:92])[CH2:77]4)[C:69]([C:94]([F:97])([F:96])[F:95])=[CH:68][N:67]=2)=[C:61]([O:98][CH3:99])[CH:60]=1)(=[O:57])[O:54]CC)[CH3:51]>>[OH:91][C@H:88]([CH2:89][OH:90])[CH2:87][N:85]1[CH:86]=[C:82]([C:79]2[CH:80]=[CH:81][C:73]([NH:72][C:70]3[C:69]([C:94]([F:97])([F:96])[F:95])=[CH:68][N:67]=[C:66]([NH:65][C:62]4[CH:63]=[CH:64][C:59]([CH2:58][P:53](=[O:54])([OH:57])[O:52][CH2:50][CH3:51])=[CH:60][C:61]=4[O:98][CH3:99])[N:71]=3)=[C:74]3[C:78]=2[CH2:77][N:76]([CH3:92])[C:75]3=[O:93])[CH:83]=[N:84]1

Participants

Reactant 2

HCID 49821942Diethyl[4-({4-[(7-{1-[(2S)-2,3-dihydroxypropyl]-1H-pyrazol-4-yl}-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)-3-methoxy benzyl]phosphonate2×

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

Product 1

HCID 86697684Ethyl hydrogen [4-({4-[(7-{1-[(2S)-2,3-dihydroxypropyl]-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 75.4%

Procedure

This material was prepared analogously to Compound 3A using diethyl[4-({4-[(7-{1-[(2S)-2,3-dihydroxypropyl]-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 5B, 254 mg, 353 μmol) to yield 184 mg of the desired product (75%). 1H NMR (400 MHz, CD3OD) δ 8.42 (br. s., 1H), 8.20 (br. s., 1H), 8.08-8.16 (m, 1H), 8.06 (br. s., 1H), 7.80 (s, 1H), 7.57 (d, J=8.6 Hz, 1H), 7.09 (br. s., 1H), 6.95 (d, J=7.8 Hz, 1H), 4.37 (dd, J=4.17, 14 Hz, 3H), 4.16-4.26 (m, 1H), 4.07 (dd, J=4.6, 7.3 Hz, 1H), 3.88-3.97 (m, 2H), 3.87 (s, 3H), 3.58 (d, J=5.3 Hz, 2H), 3.10 (br. s., 3H), 3.01-3.08 (m, 2H), 1.21 (t, J=7 Hz, 3H). MS (ESI): m/z 692.21 [M+H]+. UPLC: tR=1.10 min (UPLC-TOF: polar—3 min).

Sources & evidence

ORD record: ord-86616bee0271413c96e01ad81a58aacd
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133224B2

Reaction notes

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