Cesium carbonate → HCID 66762206, compound

HRID 474424Notes

Reaction equation

HRID 474424 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([C:12]([NH2:14])=[O:13])[CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.Cl[CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O.C(OCC)(=O)C>[N:37]1([CH2:36][CH2:35][O:1][C:2]2[CH:3]=[C:4]3[C:9](=[C:10]([C:12]([NH2:14])=[O:13])[CH:11]=2)[N:8]=[CH:7][N:6]=[C:5]3[NH:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:25])([F:26])[F:24])=[CH:19][CH:18]=2)[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 66763832HCID 66763832, compound

Product 1

HCID 66762206HCID 66762206, compoundYield 87.8%

Reagents, catalysts & solvents 4

HCID 67553Tetrabutylammonium IodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of 6-Hydroxy-4-(4-trifluoromethyl-benzylamino)-quinazoline-8-carboxylic acid amide (85 mg, 0.2 mmol) in N,N-dimethylformamide (3.0 mL) was added cesium carbonate (229 mg, 0.6 mmol). The mixture was stirred vigorously for 10-15 minutes and 4-(2-Chloro-ethyl)-morpholine hydrochloride (48 mg, 0.26 mmol) was added followed by tetrabutylammonium iodide (10 mol %). The reaction was heated to 55° C. for 16 hours and then cooled to room temperature and diluted with water (15 mL) and ethyl acetate (10 mL). The phases were separated and the aqueous phase was extracted further with ethyl acetate (3×10 mL). The combined organic phases were then washed with water, dried over sodium sulfate and concentrated to a residue that was purified by column chromatography (dichloromethane to 90% dichloromethane/9% methanol/1% ammonium hydroxide) to afford the title compound as an off-white solid (83.5 mg, 75%). LCMS (ESI) 476 (M+H)

Workup

  1. temperaturecooled to room temperature
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted further with ethyl acetate (3×10 mL)
  4. washThe combined organic phases were then washed with water
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to a residue that
  7. customwas purified by column chromatography (dichloromethane to 90% dichloromethane/9% methanol/1% ammonium hydroxide)

Sources & evidence

ORD record
ord-3af7630cdd8e420cb34779f5520de8e7
Source dataset
uspto-grants-2014_01
Patent number
US08637532B2

Reaction notes

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