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-(methyloxy)-2(1H)-quinolinone Hydrochloride

HRID 657038Notes

Reaction equation

HRID 657038 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.[O:24]1[C:33]2[CH:32]=[C:31]([CH:34]=O)[N:30]=[CH:29][C:28]=2[O:27][CH2:26][CH2:25]1.C(=O)([O-])[O-].[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)[Cl:57]>CO>[ClH:57].[O:24]1[C:33]2[CH:32]=[C:31]([CH2:34][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](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=5)[CH:14]=[CH:13][C:12]4=[O:23])[CH2:4]3)[N:30]=[CH:29][C:28]=2[O:27][CH2:26][CH2:25]1

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 688094001-{2-[(3S,4S)-3-(Aminomethyl)-4-hydroxy-1-pyrrolidinyl]ethyl}-7-(methyloxy)-2(1H)-quinolinone

Product 1

HCID 689943781-[2-((3S,4S)-3-{[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]methyl}-4-hydroxy-1-pyrrolidinyl)ethyl]-7-(methyloxy)-2(1H)-quinolinone HydrochlorideYield 45%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1-{2-[(3S,4S)-3-(Aminomethyl)-4-hydroxy-1-pyrrolidinyl]ethyl}-7-(methyloxy)-2(1H)-quinolinone (94 mg, 0.296 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)) (54 mg, 0.326 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 (197 mg, 0.884 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 (62 mg, 45%) 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-1f954238c59e4da4a37630136d753a8e
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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