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

HRID 657027Notes

Reaction equation

HRID 657027 reaction equation
[NH2:1][CH2:2][C@@H:3]1[C@H:7]([OH:8])[CH2:6][N:5]([CH2:9][CH2:10][N:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:23])[CH2:4]1.[Cl:24][C:25]1[C:34]([CH:35]=O)=[N:33][C:32]2[NH:31][C:30](=[O:37])[CH2:29][O:28][C:27]=2[CH:26]=1.C(=O)([O-])[O-].[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CO>[ClH:24].[ClH:24].[Cl:24][C:25]1[C:34]([CH2:35][NH:1][CH2:2][C@@H:3]2[C@H:7]([OH:8])[CH2:6][N:5]([CH2:9][CH2:10][N:11]3[C:20]4[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=4)[CH:14]=[CH:13][C:12]3=[O:23])[CH2:4]2)=[N:33][C:32]2[NH:31][C:30](=[O:37])[CH2:29][O:28][C:27]=2[CH:26]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 574868727-Chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehydeHCID 688094001-{2-[(3S,4S)-3-(Aminomethyl)-4-hydroxy-1-pyrrolidinyl]ethyl}-7-(methyloxy)-2(1H)-quinolinone

Product 1

HCID 689912667-chloro-6-({[((3S,4S)-4-hydroxy-1-{2-[7-(methyloxy)-2-oxo-1(2H)-quinolinyl]ethyl}-3-pyrrolidinyl)methyl]amino}methyl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one dihydrochlorideYield 87%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

1-{2-[(3S,4S)-3-(Aminomethyl)-4-hydroxy-1-pyrrolidinyl]ethyl}-7-(methyloxy)-2(1H)-quinolinone (68 mg, 0.214 mmol) and 7-chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carboxaldehyde (for a synthesis see WO2003064421, Example 15(c)) (50 mg, 0.236 mmol) were combined in anhydrous DCM (5 mL) and anhydrous MeOH (1 ml) with a spatula of solid sodium carbonate. The reaction mixture was stirred under nitrogen for 18 h then sodium triacetoxyborohydride (143 mg, 0.643 mmol) was added and stirred for 1 h. The reaction mixture was concentrated and purified to obtain the free base of the title compound as a pale oil (96 mg; 87%) after column chromatography (90:10:1:DCM:MeOH:NH4OH).

Workup

  1. stirringstirred for 1 h
  2. concentrationThe reaction mixture was concentrated
  3. custompurified

Sources & evidence

ORD record
ord-b16790efde804b48841b038931092e31
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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