Diethyl(3-methoxy-4-{[4-{[2-(methylcarbamoyl)phenyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate → Ethyl hydrogen (3-methoxy-4-{[4-{[2-(methylcarbamoyl) phenyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

HRID 1947913Notes

Reaction equation

HRID 1947913 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30](=[O:33])[NH:31][CH3:32])[C:20]([C:34]([F:37])([F:36])[F:35])=[CH:19][N:18]=2)=[C:12]([O:38][CH3:39])[CH:11]=1)(=[O:8])[O:5]CC)[CH3:2]>Cl>[CH3:39][O:38][C:12]1[CH:11]=[C:10]([CH:15]=[CH:14][C:13]=1[NH:16][C:17]1[N:22]=[C:21]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30](=[O:33])[NH:31][CH3:32])[C:20]([C:34]([F:36])([F:35])[F:37])=[CH:19][N:18]=1)[CH2:9][P:4](=[O:5])([OH:8])[O:3][CH2:1][CH3:2]

Participants

3

Reactant 1

HCID 49821766Diethyl(3-methoxy-4-{[4-{[2-(methylcarbamoyl)phenyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

Product 1

HCID 58292985Ethyl hydrogen (3-methoxy-4-{[4-{[2-(methylcarbamoyl) phenyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A solution of diethyl (3-methoxy-4-{[4-{[2-(methylcarbamoyl)phenyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate (Example 53, 44.3 mg, 0.0781 mmol) in 37% HCl (1 mL) was heated at 80° C. for a total of 3.5 h. The reaction was concentrated in vacuo. The residue was dissolved in DMSO and submitted for mass-directed purification (under basic conditions; ammonium bicarbonate buffer, pH 9). The fractions containing product were combined and concentrated in vacuo, giving the title material as a white solid, 11.6 mg (27%). 1H NMR (400 MHz, MeOD) δ ppm: 8.33 (d, J=8.3 Hz, 1H), 8.29 (s, 1H), 7.85 (d, J=8.1 Hz, 1H), 7.62 (dd, J=7.8, 1.3 Hz, 1H), 7.49 (ddd, J=8.5, 7.4, 1.5 Hz, 1H), 7.18 (td, J=7.6, 1.0 Hz, 1H), 7.05 (t, J=1.8 Hz, 1H), 6.79 (ddd, J=8.1, 2.0, 1.8 Hz, 1H), 3.89 (s, 3H), 3.79-3.88 (m, 2H), 2.96 (d, J=20.2 Hz, 2H), 2.89 (s, 3H), 1.19 (t, J=6.9 Hz, 3H). MS (ES+): m/z 540.14 (100) [MH+]. HPLC: tR=2.63 min (ZQ3, polar—5 min).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionThe residue was dissolved in DMSO
  3. customsubmitted for mass-directed purification (under basic conditions; ammonium bicarbonate buffer, pH 9)
  4. additionThe fractions containing product
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b54fe74d75e243189be647773ac52fa7
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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