Sodium Bicarbonate → HCID 178483094, compound

HRID 1984878Notes

Reaction equation

HRID 1984878 reaction equation
Cl[C:2]1[N:11]=[C:10]([N:12]([CH3:14])[CH3:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[C:15]([O:19][C:20](=[O:29])[NH:21][C@H:22]1[CH2:27][CH2:26][C@@H:25]([NH2:28])[CH2:24][CH2:23]1)([CH3:18])([CH3:17])[CH3:16].C([O-])(O)=O.[Na+]>CC(O)C>[C:15]([O:19][C:20](=[O:29])[NH:21][C@H:22]1[CH2:23][CH2:24][C@@H:25]([NH:28][C:2]2[N:11]=[C:10]([N:12]([CH3:14])[CH3:13])[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH2:26][CH2:27]1)([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 126843422-Chloro-N,N-dimethylquinazolin-4-amineHCID 178418966HCID 178418966, compound

Product 1

HCID 178483094HCID 178483094, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of (2-chloro-quinazolin-4-yl)-dimethyl-amine obtained in step B of example 1 (3.00 g, 14.4 mmol) and cis-(4-amino-cyclohexyl)-carbamic acid tert-butyl ester (3.72 g, 17.4 mmol) in 2-propanol (10 mL) was stirred at reflux for 5.5 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, 20% EtOAc in hexane) to give cis-[4-(4-dimethylamino-quinazolin-2-ylamino)-cyclohexyl]-carbamic acid tert-butyl ester including solvent (5.44 g) as a colorless oil. To a solution of the above material (5.44 g) in EtOAc (10 mL) was added 4 M hydrogen chloride in EtOAc (50 mL). The reaction mixture was stirred at ambient temperature for 2 hr, and concentrated. The residue was alkalized with saturated aqueous NaHCO3, and the precipitate was collected by filtration to give cis-N2-(4-amino-cyclohexyl)-N4,N4-dimethyl-quinazoline-2,4-diamine (2.26 g, 55%) as a white solid. The aqueous layer was extracted CHCl3 (three times). The combined organic layer was dried over MgSO4, filtered, and concentrated to give cis-N2-(4-amino-cyclohexyl)-N4,N4-diethyl-quinazoline-2,4-diamine (687 mg, 17%) as a white solid.

Workup

  1. temperatureat reflux for 5.5 days
  2. extractionthe aqueous layer was extracted with CHCl3 (three times)
  3. dry with materialThe combined organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash chromatography (NH-silica, 20% EtOAc in hexane)

Sources & evidence

ORD record
ord-80a004ffb7214a608ecaf658723da37d
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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