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 (3-chloro-4-{[4-({6-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

HRID 2279769Notes

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[CH:52]=[C:53]([CH:63]=[CH:64][C:65]=1[NH:66][C:67]1[N:72]=[C:71]([NH:73][C:74]2[C:75]([C:89](=[O:92])[NH:90][CH3:91])=[N:76][C:77]([C:80]3[CH:81]=[N:82][N:83]([CH2:85][CH2:86][CH2:87][OH:88])[CH:84]=3)=[CH:78][CH:79]=2)[C:70]([C:93]([F:96])([F:95])[F:94])=[CH:69][N:68]=1)[CH2:54][P:55](=[O:62])([O:59]CC)[O:56][CH2:57][CH3:58]>>[Cl:50][C:51]1[CH:52]=[C:53]([CH:63]=[CH:64][C:65]=1[NH:66][C:67]1[N:72]=[C:71]([NH:73][C:74]2[C:75]([C:89](=[O:92])[NH:90][CH3:91])=[N:76][C:77]([C:80]3[CH:81]=[N:82][N:83]([CH2:85][CH2:86][CH2:87][OH:88])[CH:84]=3)=[CH:78][CH:79]=2)[C:70]([C:93]([F:96])([F:94])[F:95])=[CH:69][N:68]=1)[CH2:54][P:55](=[O:59])([OH:62])[O:56][CH2:57][CH3:58]

Participants

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)phosphonate

HCID 86697724diethyl (3-chloro-4-{[4-({6-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate2×

Product 1

HCID 86697723Ethyl hydrogen (3-chloro-4-{[4-({6-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonateYield 100%

Procedure

Prepared analogously to Compound 3A using diethyl (3-chloro-4-{[4-({6-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate (Compound 24B, 176 mg, 253 μmol) to afford 169 mg of the title compound (100%). 1H NMR (400 MHz, CD3OD) δ=8.85-8.93 (m, 1H), 8.55 (s, 1H), 8.32 (s, 1H), 8.23 (s, 1H), 7.68 (d, J=9.1 Hz, 1H), 7.52-7.59 (m, 2H), 7.34 (d, J=8.01 Hz, 1H), 4.31 (t, J=6.8 Hz, 2H), 3.88 (t, J=7.1 Hz, 2H), 3.58 (t, J=6.2 Hz, 2H), 3.04 (d, J=21.0 Hz, 2H), 2.98 (s, 3H), 2.11 (t, J=6.3 Hz, 2H), 1.14 (t, J=7.1 Hz, 3H). MS (ESI): m/z=669.66 [M+H]+. UPLC: tR=1.17 min (UPLC-SQD: analytical—2 min).

Sources & evidence

ORD record: ord-b70a8b2463ec42a68e55eea5cb75a6c8
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133224B2

Reaction notes

Loading…