Sodium Sulfate → 6-{[({(3S)-1-[2-(7-fluoro-2-oxo-1(2H)-quinolinyl)ethyl]-3-pyrrolidinyl}methyl)amino]methyl}-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

HRID 657060Notes

Reaction equation

HRID 657060 reaction equation
[NH2:1][CH2:2][C@@H:3]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]([F:20])[CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:21])[CH2:4]1.[O:22]=[C:23]1[CH2:28][O:27][C:26]2[CH:29]=[CH:30][C:31]([CH:33]=O)=[N:32][C:25]=2[NH:24]1.[O-]S([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[F:20][C:17]1[CH:18]=[C:19]2[C:14]([CH:13]=[CH:12][C:11](=[O:21])[N:10]2[CH2:9][CH2:8][N:5]2[CH2:6][CH2:7][C@@H:3]([CH2:2][NH:1][CH2:33][C:31]3[CH:30]=[CH:29][C:26]4[O:27][CH2:28][C:23](=[O:22])[NH:24][C:25]=4[N:32]=3)[CH2:4]2)=[CH:15][CH:16]=1

Participants

5

Reactant 4

HCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 218737373-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehydeHCID 688179411-{2-[(3S)-3-(Aminomethyl)-1-pyrrolidinyl]ethyl}-7-fluoro-2(1H)-quinolinone

Product 1

HCID 579279906-{[({(3S)-1-[2-(7-fluoro-2-oxo-1(2H)-quinolinyl)ethyl]-3-pyrrolidinyl}methyl)amino]methyl}-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneYield 51%

Procedure

To a solution of 1-{2-[(3S)-3-(aminomethyl)-1-pyrrolidinyl]ethyl}-7-fluoro-2(1H)-quinolinone (87 mg, 0.30 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)) (54 mg, 0.302 mmol) was added Na2SO4 (355 mg, 2.50 mmol) and the reaction was stirred at ambient temperature for 18 h. The intermediate imine was treated with sodium triacetoxyborohydride (160 mg, 0.75 mmol) and stirred for an additional 16 h). The solvents were removed under reduced pressure; the residue was partitioned between dichloromethane and aqueous sodium bicarbonate, and the organic layer was dried (Na2SO4). Purification by column chromatography on silica gel, (1% to 20% methanol:dichloromethane gradient) yielded the title compound as an amorphous off-white solid (69 mg, 51%).

Workup

  1. stirringstirred for an additional 16 h)
  2. customThe solvents were removed under reduced pressure
  3. customthe residue was partitioned between dichloromethane and aqueous sodium bicarbonate
  4. dry with materialthe organic layer was dried (Na2SO4)
  5. customPurification by column chromatography on silica gel, (1% to 20% methanol:dichloromethane gradient)

Sources & evidence

ORD record
ord-e9bf17c4f9e54d65a4b30d8e2704f846
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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