1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-3-(2,2-Dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide hydrogen chloride

HRID 2097142ノート

反応式

HRID 2097142 の反応式
[CH3:1][NH:2][CH2:3][C:4]1[O:5][C:6]2[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=2[C:8]=1[CH3:9].[ClH:14].[CH3:15][C:16]1([CH3:31])[O:21][C:20]2[CH:22]=[C:23]([CH:26]=[CH:27][C:28]([OH:30])=O)[CH:24]=[N:25][C:19]=2[NH:18][CH2:17]1.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.CN(C)CCCN=C=NCC>CN(C=O)C.O>[ClH:14].[CH3:31][C:16]1([CH3:15])[O:21][C:20]2[CH:22]=[C:23](/[CH:26]=[CH:27]/[C:28]([N:2]([CH3:1])[CH2:3][C:4]3[O:5][C:6]4[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=4[C:8]=3[CH3:9])=[O:30])[CH:24]=[N:25][C:19]=2[NH:18][CH2:17]1

参加物

8

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 46785639N-methyl-1-(3-methylbenzofuran-2-yl)methanamineHCID 669677313-(2,2-dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylic acid hydrochloride

生成物 1

HCID 16659990(E)-3-(2,2-Dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide hydrogen chloride

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of methyl-(3-methyl-benzofuran-2-ylmethyl)-amine (88 mg, 0.5 mmol) in DMF (5 mL) were added in sequential order 3-(2,2-dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylic acid hydrochloride (107 mg, 0.46 mmol), 1-hydroxybenzotriazole (68 mg, 0.5 mmol), diisopropylethylamine (240 uL, 1.38 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (100 mg, 0.5 mmol). The mixture was stirred at room temperature overnight, cooled in an ice bath and water added with rapid stirring. The product was extracted with ethyl acetate (3×10 mL), dried with sodium sulfate, filtered and concentrated. The free base was re-solvated in methylene chloride (5 mL) and a solution of 4M HCl in dioxane (1 mL) was added to precipitate the hydrogen chloride salt as a pale yellow solid (84 mg, 43%): 1H NMR (400 MHz, DMSO-d6) δ 8.94 (1s, 1H), 8.01-8.06 (m, 2H), 7.47-7.58 (m, 3H), 7.16-7.25 (m, 3H), 4.73-4.94 (rotamers, 2s, 2H), 3.42 (s, 2H), 3.04 (s, 3H), 2.42 (s, 3H), 1.34 (s, 6H); MS (ESI) m/e 392 (C23H25N3O3+H)+.

後処理

  1. temperaturecooled in an ice bath
  2. extractionThe product was extracted with ethyl acetate (3×10 mL)
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additiona solution of 4M HCl in dioxane (1 mL) was added
  7. customto precipitate the hydrogen chloride salt as a pale yellow solid (84 mg, 43%)

出典と根拠

ORDレコード
ord-2c64068dde2148b298885666418cb048
出典データセット
uspto-grants-2013_05
特許番号
US08450307B2

反応ノート

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