Ethyl Acetate → HCID 59441705, compound

HRID 1014539Notes

Reaction equation

HRID 1014539 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.[CH3:32][N:33]([CH2:35][C:36]([N:38]1[C:47]2[C:42](=[CH:43][C:44]([CH3:49])=[C:45]([NH2:48])[CH:46]=2)[CH2:41][CH2:40][CH2:39]1)=[O:37])[CH3:34].[NH4+:50].[OH-].CCOC(C)=O>FC(F)(F)CO.C1COCC1>[CH3:34][N:33]([CH3:32])[CH2:35][C:36]([N:38]1[C:47]2[C:42](=[CH:43][C:44]([CH3:49])=[C:45]([NH:48][C:3]3[N:16]=[C:7]([NH:8][C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([F:18])[C:14]=4[C:15]([NH2:50])=[O:17])[C:6]4[CH:19]=[CH:20][N:21]([S:22]([C:25]5[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=5)(=[O:24])=[O:23])[C:5]=4[N:4]=3)[CH:46]=2)[CH2:41][CH2:40][CH2:39]1)=[O:37]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 14923Ammonium HydroxideHCID 59442100HCID 59442100, compoundHCID 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 59441705HCID 59441705, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 64092,2,2-TrifluoroethanolSolventHCID 8028TetrahydrofuranSolvent

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 1-[(dimethylamino)acetyl]-6-methyl-1,2,3,4-tetrahydro-7-quinolinamine (206 mg, 0.835 mmol) in 2,2,2-trifluoroethanol (50 mL) was stirred at rt for 4 days. The resulting green solution was diluted with THF (50 mL) and a 27% aqueous NH4OH solution (100 mL). The clear orange reaction mixture was stirred at rt for 5 h. EtOAc (200 mL) was added and the mixture was washed with a saturated NaCl solution (3×100 mL). The organic layer was dried (Na2SO4), concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2 to obtain 2-({2-{[1-(N,N-dimethylglycyl)-6-methyl-1,2,3,4-tetrahydro-7-quinolinyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide as a white solid (416 mg, 74%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.85-2.01 (m, 2H), 2.13 (br s, 6H), 2.16 (s, 3H), 2.32 (s, 3H), 2.76 (t, J=6.41 Hz, 2H), 3.18 (br s, 2H), 3.77 (t, J=5.77 Hz, 2H), 6.49 (d, J=4.03 Hz, 1H), 6.68 (br s, 1H), 6.88-7.01 (m, 1H), 7.11 (s, 1H), 7.15-7.38 (m, 3H), 7.70 (br s, 1H), 7.80 (d, J=7.51 Hz, 2H), 7.92 (br s, 1H), 8.02 (br s, 1H), 8.10 (d, J=8.06 Hz, 1k), 8.58 (s, 1H), 10.49 (s, 1H); ESIMS (M+H)+=671.23.

Workup

  1. washthe mixture was washed with a saturated NaCl solution (3×100 mL)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated onto Celite
  4. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-eee568892b2d4d96b4672f595020ec0c
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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