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 511345Notes

Reaction equation

HRID 511345 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:15]=[CH:16][C:17]=1[NH:18][C:19]1[N:24]=[C:23]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[C:32](=[O:35])[NH:33][CH3:34])[C:22]([C:36]([F:39])([F:38])[F:37])=[CH:21][N:20]=1)[CH2:6][P:7](=[O:14])([O:11]CC)[O:8][CH2:9][CH3:10]>Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:15]=[CH:16][C:17]=1[NH:18][C:19]1[N:24]=[C:23]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[C:32](=[O:35])[NH:33][CH3:34])[C:22]([C:36]([F:38])([F:37])[F:39])=[CH:21][N:20]=1)[CH2:6][P:7](=[O:11])([OH:14])[O:8][CH2:9][CH3:10]

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-4e75aad50f1846b58de5bc039c20182a
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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