Sodium cyanoborohydride → 6-[({1-[2-(7-Methoxy-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}amino)methyl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

HRID 1644290

Reaction equation

HRID 1644290 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:22])[CH2:4][CH2:3]1.[O:23]=[C:24]1[CH2:29][O:28][C:27]2[CH:30]=[CH:31][C:32]([CH:34]=O)=[N:33][C:26]=2[NH:25]1.C([BH3-])#N.[Na+].[Cl:40][CH:41]([Cl:43])C.CO>>[Cl:40][CH2:41][Cl:43].[CH3:17][OH:20].[NH3:1].[NH3:25].[CH3:21][O:20][C:17]1[CH:18]=[C:19]2[C:14]([CH:13]=[CH:12][C:11](=[O:22])[N:10]2[CH2:9][CH2:8][N:5]2[CH2:6][CH2:7][CH:2]([NH:1][CH2:34][C:32]3[CH:31]=[CH:30][C:27]4[O:28][CH2:29][C:24](=[O:23])[NH:25][C:26]=4[N:33]=3)[CH2:3][CH2:4]2)=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 5003444Sodium cyanoborohydrideHCID 218737373-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehydeHCID 22036585Dichloroethane methanolHCID 593982891-[2-(4-aminopiperidin-1-yl)ethyl]-7-methoxyquinolin-2(1H)-one2×

Product 2

HCID 159831906-[({1-[2-(7-Methoxy-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}amino)methyl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneHCID 86642602Dichloromethane methanol ammonia ammonia

Conditions

Temperature
0 °C

Procedure

1-[2-(4-Aminopiperidin-1-yl)ethyl]-7-methoxyquinolin-2(1H)-one (Intermediate 1, crude, 60 mg, 0.20 mmol), 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehyde (WO 2004/058144) (43 mg, 0.24 mmol) in dry dichloroethane/methanol (10 mL, 1:1) were heated over 3 Å molecular sieves at reflux for 4 hours. The reaction mixture was cooled to 0° C., and sodium cyanoborohydride (19 mg, 0.30 mmol) was added and it was stirred at room temperature for 2 hours. The mixture was filtered through a fritted funnel and concentrated to dryness under reduced pressure. The residue was taken up in ethyl acetate and washed with saturated sodium bicarbonate followed by saturated sodium chloride. The saturated sodium bicarbonate was extracted with chloroform, and the chloroform was washed with saturated sodium chloride. The ethyl acetate and chloroform extracts were combined, dried over sodium sulfate and concentrated to dryness under reduced pressure. Silica gel chromatography with dichloromethane/methanol/ammonia ammonia (8:2:0.01) gave title compound as a colorless oil, 27 mg (30%).

Workup

  1. temperatureat reflux for 4 hours
  2. filtrationThe mixture was filtered through a fritted funnel
  3. concentrationconcentrated to dryness under reduced pressure
  4. washwashed with saturated sodium bicarbonate
  5. extractionThe saturated sodium bicarbonate was extracted with chloroform
  6. washthe chloroform was washed with saturated sodium chloride
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-39c5742d0c8a43c7831488b8301f42c9
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Linked notes

Loading…