Dichloromethane → 3-(5-Methoxy-3-trifluoromethyl-phenyl)-1-{6-[3-chloro-4-(4-ethyl-piperazin-1-yl)phenylamino]-pyrimidin-4-yl}-1-methyl-urea

HRID 2066720Notes

Reaction equation

HRID 2066720 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:35]([F:38])([F:37])[F:36])[CH:6]=[C:7]([NH:9][C:10](=[O:34])[N:11]([C:13]2[CH:18]=[C:17]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:31][CH2:30][N:29]([CH2:32][CH3:33])[CH2:28][CH2:27]4)=[CH:22][CH:21]=3)[N:16]=[CH:15][N:14]=2)[CH3:12])[CH:8]=1.C([O-])(O)=O.[Na+].C(Cl)[Cl:45]>C(#N)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:35]([F:37])([F:38])[F:36])[CH:6]=[C:7]([NH:9][C:10](=[O:34])[N:11]([C:13]2[CH:18]=[C:17]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:31][CH2:30][N:29]([CH2:32][CH3:33])[CH2:28][CH2:27]4)=[C:22]([Cl:45])[CH:21]=3)[N:16]=[CH:15][N:14]=2)[CH3:12])[CH:8]=1

Participants

5

Reactant 3

HCID 6344Dichloromethane2×HCID 516892Sodium BicarbonateHCID 23630277HCID 23630277, compound

Product 1

HCID 236302483-(5-Methoxy-3-trifluoromethyl-phenyl)-1-{6-[3-chloro-4-(4-ethyl-piperazin-1-yl)phenylamino]-pyrimidin-4-yl}-1-methyl-urea

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Portions of 0.4 mL of a 1 M solution of SO2Cl2 in DCM are added repeatedly over a period of 27 h to an ice-cooled suspension of 3-(5-methoxy-3-trifluoromethyl-phenyl)-1-{6-[4-(4-ethylpiperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (105 mg, 0.20 mmol) (Example 26) in acetonitrile (6 mL). The reaction is followed by HPLC analysis. The reaction mixture (still containing starting material) is diluted with DCM and a saturated aqueous solution of NaHCO3. The aqueous layer is separated and extracted twice with DCM. The organic phases are washed with brine, dried (Na2SO4), filtered and concentrated. Reversed phase MPLC (H2O/CH3CN+0.1% TFA) yields, after neutralization of the product containing fractions with NaHCO3, partial concentration and extraction with DCM, the title compound: API-MS: 564/566 [MH]+; TLC: Rf=0.28 (DCM/MeOH+1% NH3aq, 95:5); 1H-NMR (DMXO-d6) δ 1.02 (t, H3C), 2.37 (q, H2C), 2.51 (m, 4H), 2.92 (m, 4H), 3.33 (s, H3C), 3.82 (s, H3C), 6.48 (s, 1H), 6.90 (s, 1H), 7.12 (d, 1H), 7.43 (m, 2H), 7.59 (s, 1H), 7.82 (s, 1H), 8.55 (s, 1H), 9.66 (s, HN), 12.33 (s, HN).

Workup

  1. temperaturecooled
  2. additionThe reaction mixture (still containing starting material)
  3. customThe aqueous layer is separated
  4. extractionextracted twice with DCM
  5. washThe organic phases are washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customReversed phase MPLC (H2O/CH3CN+0.1% TFA) yields
  10. additionafter neutralization of the product containing fractions
  11. concentrationwith NaHCO3, partial concentration and extraction with DCM

Sources & evidence

ORD record
ord-38ddc29b540f4a9799fa903e14366f02
Source dataset
uspto-grants-2012_10
Patent number
US08293746B2

Reaction notes

Loading…