1-Hydroxybenzotriazole → 2,3-Dihydrobenzofuran-7-carboxylic acid methyl-(2-{[3-(1-methyl-2-oxo-1,2-dihydroquinolin-6-yloxy)propyl]pyridin-4-ylmethylamino}ethyl)amide dihydrochloride

HRID 69010

Reaction equation

HRID 69010 reaction equation
N=C=N.ON1C2C=CC=CC=2N=N1.[CH3:14][N:15]1[C:24]2[C:19](=[CH:20][C:21]([O:25][CH2:26][CH2:27][CH2:28][N:29]([CH2:37][CH2:38][NH:39][CH3:40])[CH2:30][C:31]3[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=3)=[CH:22][CH:23]=2)[CH:18]=[CH:17][C:16]1=[O:41].[O:42]1[C:46]2[C:47]([C:51](O)=[O:52])=[CH:48][CH:49]=[CH:50][C:45]=2[CH2:44][CH2:43]1.C(OC(=O)C)C.[ClH:60]>C(OCC)(=O)C.C1COCC1.C(#N)C>[ClH:60].[ClH:60].[CH3:40][N:39]([CH2:38][CH2:37][N:29]([CH2:28][CH2:27][CH2:26][O:25][C:21]1[CH:20]=[C:19]2[C:24](=[CH:23][CH:22]=1)[N:15]([CH3:14])[C:16](=[O:41])[CH:17]=[CH:18]2)[CH2:30][C:31]1[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=1)[C:51]([C:47]1[C:46]2[O:42][CH2:43][CH2:44][C:45]=2[CH:50]=[CH:49][CH:48]=1)=[O:52]

Participants

9

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 160435CarbodiimideHCID 27950142,3-Dihydro-1-benzofuran-7-carboxylic acidHCID 21866389Hydrogen chloride-ethyl acetateHCID 669605791-Methyl-6-{3-[(2-methylamino-ethyl)-pyridin-4-ylmethyl-amino]-propoxy}-1H-quinolin-2-one

Product 1

HCID 706571802,3-Dihydrobenzofuran-7-carboxylic acid methyl-(2-{[3-(1-methyl-2-oxo-1,2-dihydroquinolin-6-yloxy)propyl]pyridin-4-ylmethylamino}ethyl)amide dihydrochloride

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

PS-Carbodiimide resin (1.3 g) and 1-hydroxy benzotriazole (HOBt) (230 mg) were added to acetonitrile and THF solution (4 ml+6 ml) of 1-methyl-6-{3-[(2-methylaminoethyl)pyridin-4-ylmethylamino]propoxy}-1H-quinolin-2-one (304 mg) and 2,3-dihydrobenzofuran-7-carboxylic acid (164 mg). The mixture was stirred at room temperature overnight. After the reaction mixture was filtrated and condensed under reduced pressure, the residue was purified by silica gel column chromatography (ethyl acetate:methanol=1:0→10:1). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution (0.35 ml) was added to an ethyl acetate solution of the residue. The precipitated insoluble matter was separated, washed with ethyl acetate, and dried to give the title compound (324.2 mg) as a white powder.

Workup

  1. filtrationAfter the reaction mixture was filtrated
  2. customcondensed under reduced pressure
  3. customthe residue was purified by silica gel column chromatography (ethyl acetate:methanol=1:0→10:1)
  4. customcondensed under reduced pressure
  5. customThe precipitated insoluble matter was separated
  6. washwashed with ethyl acetate
  7. customdried

Sources & evidence

ORD record
ord-56afdde03ef94cfaa7f0355ac72a4f1a
Source dataset
uspto-grants-2014_09
Patent number
US08822453B2

Linked notes

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