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

HRID 2279807Notes

Reaction equation

HRID 2279807 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.C(OP1(=O)CC2C=CC(=CC=2)NC2=NC(=C(C(F)(F)F)C=N2)NC2C=CC(=NC=2C(NC)=O)C2=CN(N=C2)CCCCO1)C.Cl[C:115]1[C:120]([C:121]([F:124])([F:123])[F:122])=[CH:119][N:118]=[C:117]([NH:125][C:126]2[CH:140]=[CH:139][C:129]([CH2:130][P:131](=[O:138])([O:135][CH2:136][CH3:137])[O:132][CH2:133][CH3:134])=[CH:128][C:127]=2[CH3:141])[N:116]=1>>[OH:65][CH2:64][CH2:63][CH2:62][N:60]1[CH:61]=[C:57]([C:54]2[N:53]=[C:52]([C:66](=[O:67])[NH:68][CH3:69])[C:51]([NH:50][C:119]3[C:120]([C:121]([F:124])([F:122])[F:123])=[CH:115][N:116]=[C:117]([NH:125][C:126]4[CH:140]=[CH:139][C:129]([CH2:130][P:131](=[O:138])([O:135][CH2:136][CH3:137])[O:132][CH2:133][CH3:134])=[CH:128][C:127]=4[CH3:141])[N:118]=3)=[CH:56][CH:55]=2)[CH:58]=[N:59]1

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-carboxamideHCID 7651826811-ethoxy-N-methyl-21-(trifluoromethyl)-10-oxa-4,5,17,19,23,26,29-heptaaza-11-phosphapentacyclo[22.2.2.213,16.12,5.118,22]dotriaconta-1(26),2(32),3,13,15,18(29),19,21,24,27,30-undecaene-25-carboxamide 11-oxideHCID 86697748Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methylbenzyl)phosphonate2×

Product 1

HCID 86697747diethyl (4-{[4-({6-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methyl benzyl)phosphonateYield 66%

Procedure

Prepared analogously to Compound 1B replacing Compound 1C with Compound 6C and Compound 1 E with diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methylbenzyl)phosphonate (Compound 33C, 339 mg, 774 μmol) to afford 345 mg of the title compound (66%). 1H NMR (400 MHz, CD3OD) δ 8.90 (br. s., 1H), 8.49 (s, 1H), 8.31 (d, J=10.1 Hz, 2H), 7.63 (d, J=9.1 Hz, 1H), 7.35-7.39 (m, 1H), 7.33 (s, 1H), 7.24-7.31 (m, 1H), 4.32 (t, J=7.0 Hz, 2H), 4.11 (quin, J=7.3 Hz, 4H), 3.56-3.61 (m, 2H), 3.33 (d, J=21.0 Hz, 2H), 3.00 (s, 3H), 2.28 (s, 3H), 2.12 (quin, J=6.5 Hz, 2H), 1.24-1.30 (m, 6H). MS (ESI): m/z=677.21 [M+H]+. UPLC: tR=1.42 min (UPLC-TOF: polar—3 min).

Sources & evidence

ORD record
ord-1835c2ed99e44614a35205f060b2b955
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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