Ammonium Chloride → N4-(4,4-difluorocyclohexyl)quinazoline-4,8-diamine

HRID 1469730

Reaction equation

HRID 1469730 reaction equation
[F:1][C:2]1([F:22])[CH2:7][CH2:6][CH:5]([NH:8][C:9]2[C:18]3[C:13](=[C:14]([N+:19]([O-])=O)[CH:15]=[CH:16][CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH2:4][CH2:3]1.[NH4+].[Cl-]>CCO.[Fe]>[F:22][C:2]1([F:1])[CH2:7][CH2:6][CH:5]([NH:8][C:9]2[C:18]3[C:13](=[C:14]([NH2:19])[CH:15]=[CH:16][CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH2:4][CH2:3]1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 71678050N-(4,4-difluorocyclohexyl)-8-nitroquinazolin-4-amine

Product 1

HCID 86692230N4-(4,4-difluorocyclohexyl)quinazoline-4,8-diamineYield 86.1%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Procedure

To a solution of N-(4,4-difluorocyclohexyl)-8-nitroquinazolin-4-amine (90 mg, 0.292 mmol) in EtOH (2 mL) were added iron powder (163 mg, 2.92 mmol) and NH4Cl (127 mg, 2.33 mmol) and the reaction mixture was heated at reflux for 2 h. Then the reaction mixture was filtered through celite. The celite bed was washed with 10% MeOH in CHCl3. The filtrate was washed with a saturated aq. NaHCO3 solution and water. The organic layer was separated, dried, filtered and concentrated to afford 70 mg of the title product. 1H NMR (300 MHz, DMSO d6): δ 8.38 (s, 1H), 7.64 (d, J=7.2 Hz, 1H), 7.35 (d, J=7.8 Hz, 1H), 7.19-7.14 (t, J=7.8 Hz, 1H), 6.87 (d, J=7.8 Hz, 1H), 5.71 (s, 2H), 4.38 (m, 1H), 2.09-1.97 (m, 6H), 1.73-1.69 (m, 2H); MS (m/z): 279.12 (M+H)+.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 2 h
  3. filtrationThen the reaction mixture was filtered through celite
  4. washThe celite bed was washed with 10% MeOH in CHCl3
  5. washThe filtrate was washed with a saturated aq. NaHCO3 solution and water
  6. customThe organic layer was separated
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c9003f49b274484295f2f9369bcce0e5
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Linked notes

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