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 409690Notes

Reaction equation

HRID 409690 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 (DMSO-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-cd827d1b10964d9ab463ca0b4d24591e
Source dataset
uspto-grants-2014_06
Patent number
US08759517B2

Reaction notes

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