Hydrochloric Acid → HCID 178483078, compound

HRID 1984929Notes

Reaction equation

HRID 1984929 reaction equation
[CH3:1][N:2]([CH3:23])[C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]=[C:5]([NH:13][C@@H:14]2[CH2:19][CH2:18][C@H:17]([C:20]([NH2:22])=O)[CH2:16][CH2:15]2)[N:4]=1.Cl>C1COCC1.CCOC(C)=O.CO>[NH2:22][CH2:20][C@@H:17]1[CH2:16][CH2:15][C@H:14]([NH:13][C:5]2[N:4]=[C:3]([N:2]([CH3:23])[CH3:1])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[N:6]=2)[CH2:19][CH2:18]1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 178483081HCID 178483081, compound

Product 1

HCID 178483078HCID 178483078, compoundYield 59%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of cis-4-(4-dimethylamino-quinazolin-2-ylamino)-cyclohexanecarboxylic acid amide (18.78 g, 60 mmol) in THF (200 mL) was added a solution of 1 M BH3 in THF (300 mL, 300 mmol). The mixture was stirred at reflux for 2 hr. After cooling the reaction mixture to 0° C., 4 M HCl in EtOAc (100 mL) and MeOH (200 mL) were added. The mixture was concentrated. The mixture was treated with 1 M aqueous sodium hydroxide and the aqueous layer was extracted with CH2Cl2. The organic layer was dried over sodium sulfate, concentrated, and purified by column chromatography (silica gel, 10% 2 M NH3/MeOH in CH2Cl2) to give cis-N2-(4-aminomethyl-cyclohexyl)-N4,N4-dimethyl-quinazoline-2,4-diamine as a white solid (10.6 g, 59%).

Workup

  1. temperatureat reflux for 2 hr
  2. concentrationThe mixture was concentrated
  3. additionThe mixture was treated with 1 M aqueous sodium hydroxide
  4. extractionthe aqueous layer was extracted with CH2Cl2
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated
  7. custompurified by column chromatography (silica gel, 10% 2 M NH3/MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-945c9266fbd840128997a2ecbf739bd3
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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