Hydrochloride methanol → 1-(3-hydroxypropyl)-N-(2-methylpropyl)-N-[(3S,5R)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]-1H-benzimidazole-2-carboxamide dihydrochloride

反応式

[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[C:6]1[C:14]([N:16]([CH2:38][CH:39]([CH3:41])[CH3:40])[C@H:17]1[CH2:22][C@@H:21]([C:23]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[O:24])[CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18]1)=[O:15].[ClH:42].CO>>[ClH:42].[ClH:42].[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[C:6]1[C:14]([N:16]([CH2:38][CH:39]([CH3:41])[CH3:40])[C@H:17]1[CH2:22][C@@H:21]([C:23]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[O:24])[CH2:20][NH:19][CH2:18]1)=[O:15]

参加物

反応物 2

HCID 21893726Hydrochloride methanol

HCID 67026033tert-butyl (3S,5R)-3-[{[1-(3-hydroxypropyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

生成物 1

HCID 673217171-(3-hydroxypropyl)-N-(2-methylpropyl)-N-[(3S,5R)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]-1H-benzimidazole-2-carboxamide dihydrochloride

実験手順

To a mixed solution of tert-butyl (3S,5R)-3-[(1H-benzimidazol-2-ylcarbonyl)(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (103 mg), propane-1,3-diol (152 mg) and triphenylphosphine (105 mg) in toluene (5 ml) and THF (5 ml) was added diisopropyl azodicarboxylate (202 μl) at room temperature, and the mixture was stirred at the same temperature for 15 hr. The reaction mixture was diluted with aqueous sodium bicarbonate, and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to basic silica gel column chromatography, and a fraction eluted with ethyl acetate was concentrated under reduced pressure to give tert-butyl (3S,5R)-3-[{[1-(3-hydroxypropyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate. The obtained tert-butyl (3S,5R)-3-[{[1-(3-hydroxypropyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate was dissolved in 10-20% hydrogen chloride-methanol (3 ml), and the mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated to give the object product (22 mg).

後処理

concentrationThe reaction mixture was concentrated

出典と根拠

ORDレコード: ord-df9c0f863a1843a69079ab1f305f5b40
出典データセット: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
特許番号: US09045436B2

反応ノート

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