HCID 86654018, compound → HCID 58293068, compound

HRID 511315Notes

Reaction equation

HRID 511315 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:34]=[CH:33][CH:32]=[C:31]3[C:27]=2[C:28](=[O:36])[N:29]([CH3:35])[CH2:30]3)[C:22]([C:37]([F:40])([F:39])[F:38])=[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:34]=[CH:33][CH:32]=[C:31]3[C:27]=2[C:28](=[O:36])[N:29]([CH3:35])[CH2:30]3)[C:22]([C:37]([F:39])([F:40])[F:38])=[CH:21][N:20]=1)[CH2:6][P:7](=[O:11])([OH:14])[O:8][CH2:9][CH3:10]

Participants

3

Reactant 1

HCID 86654018HCID 86654018, compound

Product 1

HCID 58293068HCID 58293068, compound

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A solution of diethyl [3-methoxy-4-({4-[(2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate (14.7 mg, 0.0254 mmol) in 37% HCl (1 mL) was heated at 80° C. for 3.5 h. The reaction mixture 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, yielding the title material as a white solid, 4.5 mg (32%). 1H NMR (400 MHz, MeOD) δ ppm: 8.50 (br s, 1H), 8.32 (s, 1H), 7.71 (d, J=8.1 Hz, 1H), 7.47 (t, J=8.0 Hz, 1H), 7.16 (d, J=7.3 Hz, 1H), 7.12 (t, J=1.6 Hz, 1H), 6.94 (dt, J=8.1, 1.9 Hz, 1H), 4.45 (s, 2H), 3.89 (s, 3H), 3.88 (quin, J=6.9 Hz, 2H), 3.16 (s, 3H), 3.02 (d, J=20.2 Hz, 2H), 1.20 (t, J=7.1 Hz, 3H). MS (ES+): m/z 552.15 [MH+]; HPLC: tR=2.81 min (ZQ3, polar—5 min).

Workup

  1. concentrationThe reaction mixture 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-2c5331638b434d728b9234f846b40e96
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

Loading…