Hydrochloric Acid → HCID 68997028, compound

HRID 657117Notes

Reaction equation

HRID 657117 reaction equation
[ClH:1].[NH2:2][CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][N:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([F:21])[CH:19]=3)[C:14]([C:22]#[N:23])=[CH:13][C:12]2=[O:24])[CH2:5][CH2:4]1.[O:25]=[C:26]1[CH2:31][O:30][C:29]2[CH:32]=[CH:33][C:34]([CH:36]=O)=[N:35][C:28]=2[NH:27]1.C([O-])(=O)C.[Na+].C([BH3-])#N.Cl>ClCCl.O1CCOCC1.C(O)(=O)C.C(Cl)(Cl)Cl.CO>[ClH:1].[ClH:1].[F:21][C:18]1[CH:19]=[C:20]2[C:15]([C:14]([C:22]#[N:23])=[CH:13][C:12](=[O:24])[N:11]2[CH2:10][CH2:9][N:6]2[CH2:5][CH2:4][CH:3]([NH:2][CH2:36][C:34]3[CH:33]=[CH:32][C:29]4[O:30][CH2:31][C:26](=[O:25])[NH:27][C:28]=4[N:35]=3)[CH2:8][CH2:7]2)=[CH:16][CH:17]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 498716Cyano-borohydrideHCID 517045Sodium AcetateHCID 218737373-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehydeHCID 68809836HCID 68809836, compound

Product 1

HCID 68997028HCID 68997028, compoundYield 55%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolventHCID 21584188Chloroform methanolSolvent

Procedure

To a solution of 1-[2-(4-amino-1-piperidinyl)ethyl]-7-fluoro-2-oxo-1,2-dihydro-4-quinolinecarbonitrile hydrochloride (0.062 g, 0.16 mmol) and 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carboxaldehyde (for a synthesis see WO2003087098, Example 31(e))(0.028 g, 0.16 mmol) in 1:1 chloroform/methanol (6 ml) was added sodium acetate (00.10 g, 12 mmol), acetic acid (0.5 ml) and 3A sieves and the mixture stirred for 1 h. Polymer supported cyanoborohydride (0.10 g) was added and the mixture stirred for 18 h, then filtered and the solid washed with dichloromethane. The organics were washed with sodium carbonate solution, dried and concentrated. Chromatography over silica (10 g SPE gradient elution with dichloromethane/methanol 0-15%) provided the product which was dissolved in dichloromethane and treated with 4M HCl in 1,4-dioxane. The precipitate was isolated and washed with ether then dried to provide the title compound (0.048 g, 55%).

Workup

  1. additionwas added
  2. stirringthe mixture stirred for 18 h
  3. filtrationfiltered
  4. washthe solid washed with dichloromethane
  5. washThe organics were washed with sodium carbonate solution
  6. customdried
  7. concentrationconcentrated
  8. customChromatography over silica (10 g SPE gradient elution with dichloromethane/methanol 0-15%) provided the product which
  9. customThe precipitate was isolated
  10. washwashed with ether
  11. customthen dried

Sources & evidence

ORD record
ord-c118f55342784cd9bdf040758b741ade
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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