Diethyl (4-{[4-({7-[1-(3-hydroxypropyl)-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 → diethyl (4-{[4-({2-(diethylcarbamoyl)-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

HRID 2279710Notes

Reaction equation

HRID 2279710 reaction equation
OCCCN1C=C(C2C=CC(NC3C(C(F)(F)F)=CN=C(NC4C=CC(CP(=O)(OCC)OCC)=CC=4OC)N=3)=C3C=2CN(C)C3=O)C=N1.Cl[C:51]1[C:56]([C:57]([F:60])([F:59])[F:58])=[CH:55][N:54]=[C:53]([NH:61][C:62]2[CH:76]=[CH:75][C:65]([CH2:66][P:67](=[O:74])([O:71][CH2:72][CH3:73])[O:68][CH2:69][CH3:70])=[CH:64][C:63]=2[O:77][CH3:78])[N:52]=1.[NH2:79][C:80]1[CH:92]=[CH:91][C:90]([C:93]2[CH:94]=[N:95][N:96]([CH2:98][CH2:99][CH2:100][OH:101])[CH:97]=2)=[CH:89][C:81]=1[C:82]([N:84]([CH2:87][CH3:88])[CH2:85][CH3:86])=[O:83]>>[CH2:87]([N:84]([CH2:85][CH3:86])[C:82]([C:81]1[CH:89]=[C:90]([C:93]2[CH:94]=[N:95][N:96]([CH2:98][CH2:99][CH2:100][OH:101])[CH:97]=2)[CH:91]=[CH:92][C:80]=1[NH:79][C:51]1[C:56]([C:57]([F:59])([F:58])[F:60])=[CH:55][N:54]=[C:53]([NH:61][C:62]2[CH:76]=[CH:75][C:65]([CH2:66][P:67](=[O:74])([O:68][CH2:69][CH3:70])[O:71][CH2:72][CH3:73])=[CH:64][C:63]=2[O:77][CH3:78])[N:52]=1)=[O:83])[CH3:88]

Participants

4

Reactant 3

HCID 58292892Diethyl (4-{[4-({7-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateHCID 86654002Diethyl (4-{[4-chloro-5-(trifluoromethyl) pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate2×HCID 866976802-amino-N,N-diethyl-5-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]benzamide2×

Product 1

HCID 86697679diethyl (4-{[4-({2-(diethylcarbamoyl)-4-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]phenyl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 50.1%

Procedure

Prepared analogously to Compound 1B using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 1 E, 282.1 mg, 0.62 mmol) and 2-amino-N,N-diethyl-5-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]benzamide (Compound 3C, 196.7 mg, 0.62 mmol) to afford 228 mg of the title compound (50%). 1H NMR (400 MHz, CD3OD) δ 8.33 (br. s., 1H), 8.18 (s, 1H), 7.97 (s, 1H), 7.77 (dd, J=2.02, 8.34 Hz, 1H), 7.59-7.67 (m, 2H), 7.57 (d, J=8.08 Hz, 1H), 6.97 (br. s., 1H), 6.57 (br. s., 1H), 4.32 (t, J=6.95 Hz, 2H), 3.99 (quin, J=7.14 Hz, 4H), 3.89 (s, 3H), 3.59 (t, J=6.06 Hz, 2H), 3.43-3.52 (m, 2H), 3.08-3.22 (m, 4H), 2.11 (quin, J=6.57 Hz, 2H), 1.22 (t, J=7.07 Hz, 6H), 1.11 (t, J=6.95 Hz, 3H), 0.97 (br. s., 3H). MS (ESI): m/z 734.85 [M+H]+. UPLC: tR=1.22 min (UPLC-SQD: analytical—2 min).

Sources & evidence

ORD record
ord-ba46d824f48c4707988a34728f829168
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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