Potassium Carbonate → HCID 22030734, compound

HRID 454190Notes

Reaction equation

HRID 454190 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:18](=[O:21])([O-])[O-].[K+].[K+].ClC1[C:34]2[C:29](=[CH:30][C:31]([O:37][CH2:38][CH2:39][CH2:40][N:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)=[C:32]([O:35][CH3:36])[CH:33]=2)[N:28]=[CH:27][N:26]=1.[H-].[Na+]>CN(C)C=O.C(OCC)(=O)C.O>[CH3:36][O:35][C:32]1[CH:33]=[C:34]2[C:29](=[CH:30][C:31]=1[O:37][CH2:38][CH2:39][CH2:40][N:41]1[CH2:42][CH2:43][O:44][CH2:45][CH2:46]1)[N:28]=[CH:27][N:26]=[C:18]2[O:21][C:14]1[CH:13]=[C:12]2[C:17](=[CH:16][CH:15]=1)[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10][CH2:11]2

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 10633398tert-Butyl 3,4-dihydroquinoline-1(2H)-carboxylateHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

Product 1

HCID 22030734HCID 22030734, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

6-Hydroxy-4-(1-tertbutoxycarbonyl-1,2,3,4-tetrahydroquinoline (82 mg, 0.32 mmol) was dissolved in anhydrous dimethylformamide under argon, with potassium carbonate (61 mg, 0.44 mmol) and 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (100 mg, 0.3 mmol), (prepared as described for the starting material in Example 1). No reaction occurred after 2 hours at 60° C. Sodium hydride (12 mg, 0.3 mmol) was added and the reaction mixture was heated at 120° C. for 90 minutes. The cooled mixture was poured into water and ethyl acetate. The organic phase was washed with water, brine, dried (MgSO4), filtered and the solvent evaporated. The residue was purified by flash chromatography using first dichloromethane/methanol (97/3) as solvent. Evaporation of the solvent gave 6-methoxy-7-(3-morpholinopropoxy)-4-((1-tertbutoxycarbonyl-1,2,3,4-tetrahydroquinolin-6-yl)oxy)quinazoline (115 mg, 71%) as a white solid.

Workup

  1. custom(prepared
  2. washThe organic phase was washed with water, brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent evaporated
  6. customThe residue was purified by flash chromatography
  7. customEvaporation of the solvent

Sources & evidence

ORD record
ord-dc8906df9d564b788c3d96baa50b55de
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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