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

HRID 2279847Notes

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][C:53]([N:56]1[CH:60]=[C:59]([C:61]2[N:66]=[C:65]([C:67](=[O:70])[NH:68][CH3:69])[C:64]([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)=[CH:63][CH:62]=2)[CH:58]=[N:57]1)([CH3:55])[CH3:54]>>[OH:50][CH2:51][CH2:52][C:53]([N:56]1[CH:60]=[C:59]([C:61]2[N:66]=[C:65]([C:67](=[O:70])[NH:68][CH3:69])[C:64]([NH:71][C:72]3[C:77]([C:78]([F:81])([F:79])[F:80])=[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)=[CH:63][CH:62]=2)[CH:58]=[N:57]1)([CH3:54])[CH3:55]

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 86697785diethyl (4-{[4-({6-[1-(4-hydroxy-2-methylbutan-2-yl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate2×

Product 1

HCID 86697784Ethyl hydrogen (4-{[4-({6-[1-(4-hydroxy-2-methylbutan-2-yl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateYield 79%

Procedure

Prepared analogously to Compound 3A using diethyl (4-{[4-({6-[1-(4-hydroxy-2-methylbutan-2-yl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 50B, 117 mg, 0.163 mmol) to afford 88.6 mg of the title compound (79%). 1H NMR (400 MHz, CD3OD) δ 8.76 (s, 1H), 8.35 (s, 1H), 8.11 (d, J=8.6 Hz, 1H), 7.83 (d, J=8.6 Hz, 1H), 7.50 (d, J=8.1 Hz, 1H), 6.85 (s, 1H), 6.52 (d, J=8.1 Hz, 2H), 3.72-3.98 (m, 7H), 3.15-3.25 (m, 2H), 2.94 (s, 3H), 2.30-2.43 (m, 2H), 1.77 (s, 6H), 1.11 (t, J=7.1 Hz, 3H). MS (ESI): m/z=693.61 [M+H]+. UPLC: tR=1.18 min (UPLC-TOF: polar—2 min).

Sources & evidence

ORD record: ord-356cb616d72d42cb9358a6e2bb087dcb
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133224B2

Reaction notes

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