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 (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 2279770Notes

Reaction equation

HRID 2279770 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.[NH2:50][C:51]1[C:52]([C:66]([NH:68][CH3:69])=[O:67])=[N:53][C:54]([C:57]2[CH:58]=[N:59][N:60]([CH2:62][CH2:63][CH2:64][OH:65])[CH:61]=2)=[CH:55][CH:56]=1.ClC1C(C(F)(F)F)=CN=C(NC2C=CC(CP(=O)(OCC)OCC)=CC=2OC)N=1.[Cl:99][C:100]1[CH:101]=[C:102]([CH:112]=[CH:113][C:114]=1[NH:115][C:116]1[N:121]=[C:120](Cl)[C:119]([C:123]([F:126])([F:125])[F:124])=[CH:118][N:117]=1)[CH2:103][P:104](=[O:111])([O:108][CH2:109][CH3:110])[O:105][CH2:106][CH3:107]>>[Cl:99][C:100]1[CH:101]=[C:102]([CH:112]=[CH:113][C:114]=1[NH:115][C:116]1[N:117]=[C:118]([NH:50][C:51]2[C:52]([C:66](=[O:67])[NH:68][CH3:69])=[N:53][C:54]([C:57]3[CH:58]=[N:59][N:60]([CH2:62][CH2:63][CH2:64][OH:65])[CH:61]=3)=[CH:55][CH:56]=2)[C:119]([C:123]([F:126])([F:124])[F:125])=[CH:120][N:121]=1)[CH2:103][P:104](=[O:111])([O:108][CH2:109][CH3:110])[O:105][CH2:106][CH3:107]

Participants

5

Reactant 4

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 678187943-amino-6-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-N-methylpyridine-2-carboxamide2×HCID 86654002Diethyl (4-{[4-chloro-5-(trifluoromethyl) pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateHCID 86697725Diethyl (3-chloro-4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate2×

Product 1

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)phosphonateYield 25%

Procedure

Prepared analogously to Compound 1B replacing Compound 1C with 3-amino-6-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-n-methylpyridine-2-carboxamide (Compound 6C, 278 mg, 1.01 mmol) and Compound 1E with diethyl (3-chloro-4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate (Compound 24C, 463 mg, 1.01 mmol) to afford 176 mg of the title compound (25%). 1H NMR (400 MHz, CD3OD) δ=8.64-8.79 (m, 1H), 8.55 (s, 1H), 8.44 (s, 1H), 8.35 (s, 1H), 7.73 (d, J=9.1 Hz, 1H), 7.65 (t, J=2.3 Hz, 1H), 7.60 (d, J=8.3 Hz, 1H), 7.44-7.49 (m, 1H), 4.28-4.35 (m, 2H), 4.08-4.18 (m, 4H), 3.56 (t, J=6.2 Hz, 2H), 3.42 (d, J=21.0 Hz, 2H), 3.00 (s, 3H), 2.11 (quin, J=6.5 Hz, 2H), 1.26 (t, J=7.1 Hz, 6H). MS (ESI): m/z=697.72 [M+H]+. UPLC: tR=1.28 min (UPLC-SQD: analytical—2 min).

Sources & evidence

ORD record
ord-74c4bc0d3ff74e65bb41bab830688659
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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