Dichloromethane → 1-[2-((3S,4S)-3-{[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]methyl}-4-hydroxy-1-pyrrolidinyl)ethyl]-7-fluoro-1,5-naphthyridin-2(1H)-one Hydrochloride

HRID 657050Notes

Reaction equation

HRID 657050 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.[O:23]1[C:32]2[CH:31]=[C:30]([CH:33]=O)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1.C(=O)([O-])[O-].[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)[Cl:56]>CO>[ClH:56].[O:23]1[C:32]2[CH:31]=[C:30]([CH2:33][NH:1][CH2:2][C@@H:3]3[C@H:7]([OH:8])[CH2:6][N:5]([CH2:9][CH2:10][N:11]4[C:20]5[C:15](=[N:16][CH:17]=[C:18]([F:21])[CH:19]=5)[CH:14]=[CH:13][C:12]4=[O:22])[CH2:4]3)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 688098161-{2-[(3S,4S)-3-(aminomethyl)-4-hydroxy-1-pyrrolidinyl]ethyl}-7-fluoro-1,5-naphthyridin-2(1H)-one

Product 1

HCID 689672341-[2-((3S,4S)-3-{[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]methyl}-4-hydroxy-1-pyrrolidinyl)ethyl]-7-fluoro-1,5-naphthyridin-2(1H)-one HydrochlorideYield 28%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1-{2-[(3S,4S)-3-(Aminomethyl)-4-hydroxy-1-pyrrolidinyl]ethyl}-7-fluoro-1,5-naphthyridin-2(1H)-one (110 mg, 0.359 mmol) and 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carboxaldehyde (for a synthesis see WO2004058144, Example 2(c) or WO03/087098, Example 19(d)) (65 mg; 0.395 mmol) were combined in anhydrous DCM (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 (239 mg, 1.08 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 (46 mg, 28%) 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-5309dee7f4f84b9a93f21edd04824755
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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