Sodium Carbonate → 7-chloro-6-{[({(3S,4S)-1-[2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl]-4-hydroxy-3-pyrrolidinyl}methyl)amino]methyl}-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one Hydrochloride

HRID 657049Notes

Reaction equation

HRID 657049 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](=[N:16][CH:17]=[C:18]([F:21])[CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:22])[CH2:4]1.[Cl:23][C:24]1[C:33]([CH:34]=O)=[N:32][C:31]2[NH:30][C:29](=[O:36])[CH2:28][O:27][C:26]=2[CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CO>[ClH:23].[Cl:23][C:24]1[C:33]([CH2:34][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](=[N:16][CH:17]=[C:18]([F:21])[CH:19]=4)[CH:14]=[CH:13][C:12]3=[O:22])[CH2:4]2)=[N:32][C:31]2[NH:30][C:29](=[O:36])[CH2:28][O:27][C:26]=2[CH:25]=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 688098161-{2-[(3S,4S)-3-(aminomethyl)-4-hydroxy-1-pyrrolidinyl]ethyl}-7-fluoro-1,5-naphthyridin-2(1H)-one

Product 1

HCID 689929617-chloro-6-{[({(3S,4S)-1-[2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl]-4-hydroxy-3-pyrrolidinyl}methyl)amino]methyl}-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one HydrochlorideYield 43%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

1-{2-[(3S,4S)-3-(Aminomethyl)-4-hydroxy-1-pyrrolidinyl]ethyl}-7-fluoro-1,5-naphthyridin-2(1H)-one (118 mg, 0.386 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)) (90 mg, 0.425 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 (257 mg, 1.16 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 yellow oil (83 mg; 43%) 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-6f4ef60cee0b49ce951e51fff38dbbf4
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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