Dimethylacetamide → HCID 178483093, compound

HRID 1984902Notes

Reaction equation

HRID 1984902 reaction equation
CC(N(C)C)=O.[F:7][C:8]([F:20])([F:19])[O:9][C:10]1[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=1[C:12]([Cl:14])=[O:13].[NH2:21][C@@H:22]1[CH2:27][CH2:26][C@H:25]([NH:28][C:29]2[N:38]=[C:37]([N:39]([CH2:42]C)[CH2:40]C)[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]=2)[CH2:24][CH2:23]1>C(Cl)Cl>[ClH:14].[CH3:40][N:39]([CH3:42])[C:37]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]=[C:29]([NH:28][C@@H:25]2[CH2:26][CH2:27][C@H:22]([NH:21][C:12](=[O:13])[C:11]3[CH:15]=[CH:16][CH:17]=[CH:18][C:10]=3[O:9][C:8]([F:20])([F:19])[F:7])[CH2:23][CH2:24]2)[N:38]=1

Participants

5

Reactant 3

HCID 31374DimethylacetamideHCID 27772412-(Trifluoromethoxy)benzoyl ChlorideHCID 178463885HCID 178463885, compound

Product 1

HCID 178483093HCID 178483093, compoundYield 27.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of polymer supported DMA (2.45 g, 7.35 mmol) in CH2Cl2 (6 mL) were added 2-trifluoromethoxy-benzoyl chloride (472 mg, 2.10 mmol) and cis-N2-(4-amino-cyclohexyl)-N4,N4-dimethylquiazoline-2,4-diamine obtained in step C of example 9 (300 mg, 1.05 mmol). The mixture was stirred at ambient temperature for 24 h, filtered, poured into saturated aqueous NaHCO3. The aqueous layer was extracted with CHCl3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated, purified by medium-pressure liquid chromatography (NH-silica gel, 25% EtOAc in hexane), and concentrated. To a solution of the residue in EtOAc (1 mL) was added 4 M hydrogen chloride in EtOAc (10 mL). The reaction mixture was stirred at ambient temperature for 1 hr, and concentrated. A solution of the residue in Et2O (10 mL) was stirred at ambient temperature for 1 hr and the precipitate was collected by filtration to give cis-N-[4-(4-dimethylaminoquinazolin-2-ylamino)-cyclohexyl]-2-trifluoromethoxy-benzamide hydrochloride (145 mg, 27%) as a white solid.

Workup

  1. additionTo a suspension of polymer
  2. filtrationfiltered
  3. additionpoured into saturated aqueous NaHCO3
  4. extractionThe aqueous layer was extracted with CHCl3 (three times)
  5. dry with materialThe combined organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by medium-pressure liquid chromatography (NH-silica gel, 25% EtOAc in hexane)
  9. concentrationconcentrated
  10. additionTo a solution of the residue in EtOAc (1 mL) was added 4 M hydrogen chloride in EtOAc (10 mL)
  11. stirringThe reaction mixture was stirred at ambient temperature for 1 hr
  12. concentrationconcentrated
  13. stirringA solution of the residue in Et2O (10 mL) was stirred at ambient temperature for 1 hr
  14. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-c6384320936c49d3a2964921a45a3162
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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