Sodium Bicarbonate → HCID 178483073, compound

HRID 1984892Notes

Reaction equation

HRID 1984892 reaction equation
[C:1]([O:5][C:6](=[O:26])[NH:7][C@H:8]1[CH2:13][CH2:12][C@@H:11]([CH2:14][NH:15][C:16](OCC2C=CC=CC=2)=O)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].ClC1[N:37]=[C:36]([N:38]([CH3:40])[CH3:39])[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[N:29]=1.C([O-])(O)=O.[Na+]>CO.CC(O)C.[Pd]>[C:1]([O:5][C:6](=[O:26])[NH:7][C@H:8]1[CH2:9][CH2:10][C@@H:11]([CH2:14][NH:15][C:16]2[N:37]=[C:36]([N:38]([CH3:40])[CH3:39])[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]=2)[CH2:12][CH2:13]1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 126843422-Chloro-N,N-dimethylquinazolin-4-amineHCID 178453948HCID 178453948, compound

Product 1

HCID 178483073HCID 178483073, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of cis-[4-(benzyloxycarbonylamino-methyl)-cyclohexyl]-carbamic acid tert-butyl ester (4.00 g, 11.0 mmol) and 5% Pd/C (400 mg) in MeOH (40 mL) was stirred under hydrogen atmosphere at ambient temperature for 8.5 hr and at 50° C. for 12 hr, filtered through a pad of celite, and concentrated. The precipitate was suspended in hexane and the suspension was stirred at ambient temperature for 30 min. The solid was collected by filtration, washed with hexane, and dried (3.03 g). A mixture of (2-chloro-quinazolin-4-yl)-dimethyl-amine obtained in step B of example 1 (1.00 g, 4.82 mmol) and the above solid (1.65 g, 7.23 mmol) in 2-propanol (10 mL) was stirred at reflux for 5 days, poured into saturated aqueous NaHCO3, and the aqueous layer was extracted with CHCl3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated, and purified by flash chromatography (NH-silica gel, 20% EtOAc in hexane) to give cis-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-cyclohexyl}-carbamic acid tert-butyl ester (629 mg, 43%) as a pale yellow solid.

Workup

  1. filtrationfiltered through a pad of celite
  2. concentrationconcentrated
  3. stirringthe suspension was stirred at ambient temperature for 30 min
  4. filtrationThe solid was collected by filtration
  5. washwashed with hexane
  6. customdried (3.03 g)
  7. temperatureat reflux for 5 days
  8. extractionthe aqueous layer was extracted with CHCl3 (three times)
  9. dry with materialThe combined organic layer was dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. custompurified by flash chromatography (NH-silica gel, 20% EtOAc in hexane)

Sources & evidence

ORD record
ord-6b57b8c803cb45e5bed2c80ff76e486a
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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