Methylamine → HCID 59441920, compound

HRID 1014537Notes

Reaction equation

HRID 1014537 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].[CH3:49][NH2:50]>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]([NH:50][CH3:49])=[O:17])[C:6]3[CH:19]=[CH:20][N:21]([S:22]([C:25]4[CH:26]=[CH:27][C:28]([CH3:31])=[CH:29][CH:30]=4)(=[O:24])=[O:23])[C:5]=3[N:4]=2)[CH:35]=1)=[O:48]

Participants

6

Reactant 3

HCID 6329MethylamineHCID 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 59441920HCID 59441920, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 64092,2,2-TrifluoroethanolSolventHCID 8028TetrahydrofuranSolvent

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 was stirred at rt. After 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 treated with a MeNH2 solution (2M in THF, 20 mL). The reaction mixture was stirred at it for 20 h, then 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-fluoro-N-methylbenzamide as a yellow solid (487 mg, 88%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.25 (s, 6H), 2.31 (s, 3H), 2.68 (d, J=4.58 Hz, 3H), 3.04 (s, 2H), 3.83 (s, 3H), 6.67 (d, J=4.03 Hz, 1H), 6.96-7.09 (m, 2H), 7.34 (d, J=8.42 Hz, 2H), 7.37-7.45 (m, 2H), 7.53 (dd, J=8.79, 2.56 Hz, 1H), 7.83 (d, J=8.24 Hz, 1H), 7.88-8.00 (m, 3H), 8.39 (br s, 1H), 8.44-8.54 (m, 1H), 9.50 (s, 1H), 10.09 (s, 1H); ESIMS (M+H)+=661.

Workup

  1. customAfter 3 days LCMS indicated incomplete reaction
  2. temperatureto cool to rt the reaction mixture
  3. concentrationconcentrated onto Celite
  4. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-58242b7b451c4768b0391dca178c75cb
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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