Sodium Chloride → t-Butyl {3-[6,7-dimethoxy-2-(methylamino)quinazolin-4-yl]phenyl}carbamate

HRID 1893992Notes

Reaction equation

HRID 1893992 reaction equation
Cl[C:2]1[N:11]=[C:10]([C:12]2[CH:13]=[C:14]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH:15]=[CH:16][CH:17]=2)[C:9]2[C:4](=[CH:5][C:6]([O:28][CH3:29])=[C:7]([O:26][CH3:27])[CH:8]=2)[N:3]=1.[CH3:30][NH2:31].[Cl-].[Na+]>O1CCCC1.C(OCC)(=O)C.CO.CC(O)C>[CH3:27][O:26][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][C:6]=1[O:28][CH3:29])[N:3]=[C:2]([NH:31][CH3:30])[N:11]=[C:10]2[C:12]1[CH:13]=[C:14]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH:15]=[CH:16][CH:17]=1

Participants

8

Reactant 3

HCID 5234Sodium ChlorideHCID 6329MethylamineHCID 86650315t-Butyl [3-(2-chloro-6,7-dimethoxyquinazolin-4-yl)phenyl]carbamate

Product 1

HCID 66669202t-Butyl {3-[6,7-dimethoxy-2-(methylamino)quinazolin-4-yl]phenyl}carbamateYield 83.8%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

In a SUS autoclave were placed 420 mg (1.00 mmol) of t-butyl [3-(2-chloro-6,7-dimethoxyquinazolin-4-yl)phenyl]carbamate, tetrahydrofuran (2.5 mL), and 2-propanol (1.25 mL), to this mixture was added a methanol solution (2.5 mL) of 40% methylamine, and the mixture was stirred at 90° C. for 8 hours. The reaction mixture was allowed to cool and then poured into a mixed solution of ethyl acetate (40 mL), tetrahydrofuran (40 mL), and 5% w/w sodium chloride solution (50 mL) to extract the organic layer. The organic layer was washed with 5% w/w sodium chloride solution (50 mL) and then concentrated under reduced pressure. To the concentration residue was added t-butyl methyl ether (2.1 mL), and the mixture was crystallized with a spatula and then stirred at room temperature for 3 hours. The precipitated crystals were collected by filtration and dried to give 348 mg of a target product (yield: 83.8%, HPLC purity: 98.70%).

Workup

  1. temperatureto cool
  2. extractionto extract the organic layer
  3. washThe organic layer was washed with 5% w/w sodium chloride solution (50 mL)
  4. concentrationconcentrated under reduced pressure
  5. additionTo the concentration residue was added t-butyl methyl ether (2.1 mL)
  6. customthe mixture was crystallized with a spatula
  7. stirringstirred at room temperature for 3 hours
  8. filtrationThe precipitated crystals were collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-cad49d56e70940c0ba40c68dcdb5f42e
Source dataset
uspto-grants-2013_08
Patent number
US08513269B2

Reaction notes

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