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

HRID 69011

反応式

HRID 69011 の反応式
[ClH:1].CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.Cl.Cl.Cl.[CH3:26][NH:27][CH2:28][CH2:29][N:30]([CH2:46][C:47]1[CH:52]=[CH:51][N:50]=[CH:49][CH:48]=1)[CH2:31][CH2:32][CH2:33][O:34][C:35]1[CH:36]=[C:37]2[C:42](=[CH:43][CH:44]=1)[C:41](=[O:45])[NH:40][CH2:39][CH2:38]2.[O:53]1[C:57]2[C:58]([C:62](O)=[O:63])=[CH:59][CH:60]=[CH:61][C:56]=2[CH2:55][CH2:54]1.C(OC(=O)C)C.Cl>C(OCC)(=O)C.O.CN(C=O)C>[ClH:1].[ClH:1].[CH3:26][N:27]([CH2:28][CH2:29][N:30]([CH2:31][CH2:32][CH2:33][O:34][C:35]1[CH:36]=[C:37]2[C:42](=[CH:43][CH:44]=1)[C:41](=[O:45])[NH:40][CH2:39][CH2:38]2)[CH2:46][C:47]1[CH:48]=[CH:49][N:50]=[CH:51][CH:52]=1)[C:62]([C:58]1[C:57]2[O:53][CH2:54][CH2:55][C:56]=2[CH:61]=[CH:60][CH:59]=1)=[O:63]

参加物

9

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27950142,3-Dihydro-1-benzofuran-7-carboxylic acidHCID 21866389Hydrogen chloride-ethyl acetateHCID 669612116-{3-[(2-methylaminoethyl)pyridin-4-ylmethylamino]propoxy}-3,4-dihydro-2H-isoquinolin-1-one trihydrochloride

生成物 1

HCID 867626802,3-Dihydrobenzofuran-7-carboxylic acid methyl-(2-{[3-(1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yloxy)propyl]pyridin-4-ylmethylamino}ethyl)amide dihydrochloride収率 74.6%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (WSC)(144 mg), and 1-hydroxy benzotriazole (HOBt)(115 mg) were added to a DMF solution (5 ml) of 6-{3-[(2-methylaminoethyl)pyridin-4-ylmethylamino]propoxy}-3,4-di hydro-2H-isoquinolin-1-one trihydrochloride (234 mg), and 2,3-dihydrobenzofuran-7-carboxylic acid (123 mg). The mixture was stirred at room temperature overnight. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was washed with water, and dried with anhydrous sodium sulfate. After condensation under reduced pressure, the residue was purified by NH 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 (0.19 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 (164.6 mg) as a white powder.

後処理

  1. extractionfollowed by extraction
  2. washThe organic layer was washed with water
  3. dry with materialdried with anhydrous sodium sulfate
  4. customAfter condensation under reduced pressure
  5. customthe residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=1:0→10:1)
  6. customcondensed under reduced pressure
  7. customThe precipitated insoluble matter was separated
  8. washwashed with ethyl acetate
  9. customdried

出典と根拠

ORDレコード
ord-3ed03c937910480798e2baa42c6f8684
出典データセット
uspto-grants-2014_09
特許番号
US08822453B2

関連ノート

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