Di-tert-butyl dicarbonate → HCID 68850126, compound

HRID 1984918Notes

Reaction equation

HRID 1984918 reaction equation
C([N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]1)C1C=CC=CC=1.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.Cl[C:31]1[N:40]=[C:39]([N:41]([CH3:43])[CH3:42])[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[N:32]=1>C1COCC1.CC(O)C>[NH2:14][CH:11]1[CH2:12][CH2:13][N:8]([C:31]2[N:40]=[C:39]([N:41]([CH3:43])[CH3:42])[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:32]=2)[CH2:9][CH2:10]1

Participants

6

Reactant 3

HCID 90495Di-tert-butyl dicarbonateHCID 4158521-Benzyl-4-piperidylamineHCID 126843422-Chloro-N,N-dimethylquinazolin-4-amine

Product 1

HCID 68850126HCID 68850126, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-benzyl-piperidin-4-ylamine (2.00 g, 10.5 mmol) in THF (20 mL) was added (Boc)2O (2.52 g, 11.5 mmol). The mixture was stirred at ambient temperature for 40 min, and concentrated. To a solution of the residue in MeOH (20 mL) was added 20% Pd(OH)2 (400 mg). The mixture was stirred at ambient temperature under hydrogen atmosphere for 20 hr. Additionally, 20% Pd(OH)2 (400 mg) was added and the mixture was stirred at ambient temperature under hydrogen atmosphere for 7 hr, at 50° C. for 4.5 hr, and at ambient temperature for 12 hr, filtered through a pad of celite, and concentrated to give a white solid. A mixture of (2-chloro-quinazolin-4-yl)-dimethyl-amine obtained in step B of example 1 (1.10 g, 5.30 mmol) and the above solid (1.27 g, 6.34 mmol) in 2-propanol (11 mL) was stirred at reflux for 20 hr. The precipitate was collected by filtration, washed with 2-propanol, dissolved in 50% MeOH in CHCl3 (60 mL). The solution was 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, EtOAc to CHCl3) to give [2-(4-amino-piperidin-1-yl)-quinazolin-4-yl]-dimethyl-amine (864 mg, 68%) as a colorless oil.

Workup

  1. concentrationconcentrated
  2. additionTo a solution of the residue in MeOH (20 mL) was added 20% Pd(OH)2 (400 mg)
  3. stirringThe mixture was stirred at ambient temperature under hydrogen atmosphere for 20 hr
  4. additionAdditionally, 20% Pd(OH)2 (400 mg) was added
  5. stirringthe mixture was stirred at ambient temperature under hydrogen atmosphere for 7 hr, at 50° C. for 4.5 hr
  6. waitat ambient temperature for 12 hr
  7. filtrationfiltered through a pad of celite
  8. concentrationconcentrated
  9. customto give a white solid
  10. temperatureat reflux for 20 hr
  11. filtrationThe precipitate was collected by filtration
  12. washwashed with 2-propanol
  13. dissolutiondissolved in 50% MeOH in CHCl3 (60 mL)
  14. additionThe solution was poured into saturated aqueous NaHCO3
  15. extractionthe aqueous layer was extracted with CHCl3 (three times)
  16. dry with materialThe combined organic layer was dried over MgSO4
  17. filtrationfiltered
  18. concentrationconcentrated
  19. custompurified by flash chromatography (NH-silica gel, EtOAc to CHCl3)

Sources & evidence

ORD record
ord-76e4ca32ab65447db256b0a1dbba8795
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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