Chloroform → HCID 59441932, compound

HRID 1014535Notes

Reaction equation

HRID 1014535 reaction equation
Cl.Cl[C:3]1[N:16]2[C:7](=[N:8][C:9]3[C:14]([C:15]2=[O:17])=[C:13]([F:18])[CH:12]=[CH:11][CH:10]=3)[C:6]2[CH:19]=[CH:20][N:21]([S:22]([C:25]3[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=3)(=[O:24])=[O:23])[C:5]=2[N:4]=1.Cl.[NH2:33][C:34]1[CH:35]=[C:36]([NH:42][C:43](=[O:48])[CH2:44][N:45]([CH3:47])[CH3:46])[CH:37]=[CH:38][C:39]=1[O:40][CH3:41].[NH4+:49].[OH-].C(Cl)(Cl)Cl>C1COCC1.FC(F)(F)CO>[CH3:46][N:45]([CH3:47])[CH2:44][C:43]([NH:42][C:36]1[CH:37]=[CH:38][C:39]([O:40][CH3:41])=[C:34]([NH:33][C:3]2[N:16]=[C:7]([NH:8][C:9]3[CH:10]=[CH:11][CH:12]=[C:13]([F:18])[C:14]=3[C:15]([NH2:49])=[O:17])[C:6]3[CH:19]=[CH:20][N:21]([S:22]([C:25]4[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=4)(=[O:24])=[O:23])[C:5]=3[N:4]=2)[CH:35]=1)=[O:48]

Participants

7

Reactant 4

HCID 6212ChloroformHCID 14923Ammonium HydroxideHCID 67315900HCID 67315900, compound2×HCID 673162535-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one HCl salt

Product 1

HCID 59441932HCID 59441932, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 64092,2,2-TrifluoroethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
80 °C

Procedure

A slurry of 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one hydrogen chloride (400 mg, 0.835 mmol) and N1-[3-amino-4-(methyloxy)phenyl]-N2,N2-dimethylglycinamide hydrogen chloride (217 mg, 0.835 mmol) in THF (15 mL) in 2,2,2-trifluoroethanol (40 mL) was stirred at rt for 3 days. LCMS indicated incomplete reaction, therefore more N1-[3-amino-4-(methyloxy)phenyl]-N2,N2-dimethylglycinamide hydrogen chloride (115 mg, 0.24 mmol) was added and the reaction mixture was heated at 80° C. for 4 h. After allowing to cool to rt the reaction mixture was diluted with THF (100 mL) and a 27% aqueous NH4OH solution (100 mL) and stirred at rt. After 20 h CHCl3 (200 mL) was added. The organic layer was washed with a saturated NaCl solution (100 mL), concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2 to obtain 2-({2-{[5-[(N,N-dimethylglycyl)amino]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide as a white solid (364 mg, 67%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.25 (s, 6H), 2.32 (s, 3H), 3.03 (s, 2H), 3.81 (s, 3H), 6.60 (d, J=4.03 Hz, 1H), 6.97-7.07 (m, 2H), 7.30-7.46 (m, 4H), 7.51 (dd, J=8.79, 2.56 Hz, 1H), 7.87-8.03 (m, 6H), 8.35 (br s, 1H), 9.50 (s, 1H), 10.38 (s, 1H); ESIMS (M+H)+=647.

Workup

  1. customreaction
  2. temperatureto cool to rt the reaction mixture
  3. washThe organic layer was washed with a saturated NaCl solution (100 mL)
  4. concentrationconcentrated onto Celite
  5. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-82b1e48346cb48ba8478864a02245487
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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