Diethyl[(4-aminophenyl)(difluoro)methyl]-phosphonate → Diethyl[difluoro(4-{[4-{[2-(methylcarbamoyl)phenyl]amino}-5-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)methyl]phosphonate

HRID 1947990Notes

Reaction equation

HRID 1947990 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:19]([F:22])([F:21])[F:20])=[CH:4][N:3]=1.[CH2:23]([O:25][P:26]([C:31]([C:34]1[CH:39]=[CH:38][C:37]([NH2:40])=[CH:36][CH:35]=1)([F:33])[F:32])(=[O:30])[O:27][CH2:28][CH3:29])[CH3:24]>>[CH2:23]([O:25][P:26]([C:31]([F:33])([F:32])[C:34]1[CH:39]=[CH:38][C:37]([NH:40][C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=3[C:11](=[O:12])[NH:13][CH3:14])[C:5]([C:19]([F:22])([F:21])[F:20])=[CH:4][N:3]=2)=[CH:36][CH:35]=1)(=[O:30])[O:27][CH2:28][CH3:29])[CH3:24]

Participants

3

Reactant 2

HCID 21088750Diethyl[(4-aminophenyl)(difluoro)methyl]-phosphonate2×HCID 866338612-((2-Chloro-5-(trifluoromethyl)pyrimidin-4-yl)amino)-N-methylbenzamide2×

Product 1

HCID 58293031Diethyl[difluoro(4-{[4-{[2-(methylcarbamoyl)phenyl]amino}-5-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)methyl]phosphonateYield 6%

Procedure

The title product was prepared according to the procedure for Example 102 2-{[2-chloro-5-(trifluoromethyl)pyrimidin-4-yl]amino}-N-methylbenzamide (Compound 104A, 40.0 mg, 0.12 mmol) and diethyl[(4-aminophenyl)(difluoro)methyl]-phosphonate (Compound 188A, 40.5 mg, 0.15 mmol). The crude product was purified by silica gel chromatography (5% 7 N NH3 in MeOH in DCM) to afford the desired product as a white solid (4.1 mg, yield: 6%). 1H NMR (CD3OD, 400 MHz): δ=1.32 (t, J=7.2 Hz, 6H), 2.90 (s, 3H), 4.14-4.25 (m, 4H), 7.22 (t, J=8.4 Hz, 1H), 7.45 (d, J=8.4 Hz, 2H), 7.51 (dt, J=1.2, 7.2 Hz, 1H), 7.66 (dd, J=1.2, 7.6 Hz, 1H), 7.79 (d, J=8.8 Hz, 2), 8.39 (s, 1H), 8.47 (d, J=8.4 Hz, 1H). MS (ES+): m/z 574.12 [MH+]. HPLC: tR=4.13 min (OpenLynx, polar—5 min).

Workup

  1. customThe title product was prepared
  2. customThe crude product was purified by silica gel chromatography (5% 7 N NH3 in MeOH in DCM)

Sources & evidence

ORD record
ord-ef01baf062334bf19f7f97263db0e12f
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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