1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-N-((5-fluoro-3-methylbenzo[b]thiophen-2-yl)methyl)-N-methyl-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylamide

HRID 2097151ノート

反応式

HRID 2097151 の反応式
[F:1][C:2]1[CH:14]=[CH:13][C:5]2[S:6][C:7]([CH2:10][NH:11][CH3:12])=[C:8]([CH3:9])[C:4]=2[CH:3]=1.[O:15]=[C:16]1[CH2:21][O:20][C:19]2[CH:22]=[C:23](/[CH:26]=[CH:27]/[C:28]([OH:30])=O)[CH:24]=[N:25][C:18]=2[NH: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>[F:1][C:2]1[CH:14]=[CH:13][C:5]2[S:6][C:7]([CH2:10][N:11]([CH3:12])[C:28](=[O:30])/[CH:27]=[CH:26]/[C:23]3[CH:24]=[N:25][C:18]4[NH:17][C:16](=[O:15])[CH2:21][O:20][C:19]=4[CH:22]=3)=[C:8]([CH3:9])[C:4]=2[CH:3]=1

参加物

8

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57742058(E)-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylic acidHCID 59456918(5-fluoro-3-methylbenzo[b]thiophen-2-yl)-N-methylmethanamine

生成物 1

HCID 16660979(E)-N-((5-fluoro-3-methylbenzo[b]thiophen-2-yl)methyl)-N-methyl-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylamide収率 13%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of (5-fluoro-3-methylbenzo[b]thiophen-2-yl)-N-methyl methanamine (200 mg, 0.96 mmol) in DMF (5 mL) were added in sequential order (E)-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylic acid (185 mg, 0.87 mmol), 1-hydroxybenzotriazole (133 mg, 0.96 mmol), diisopropylethylamine (454 uL, 2.61 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (192 mg, 0.96 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 crude product was purified using preparative HPLC to give the title compound (45 mg, 13%): 1H NMR (400 MHz, DMSO-d6) δ 11.42 (bs, 1H), 8.19 (s, 1H), 7.89-7.87 (m, 2H), 7.55-7.51 (m, 2H), 7.22-7.18 (m, 2H), 5.12-4.87 (2s, 2H, rotamers), 4.68 (s, 2H), 3.54 (s, 3H), 2.39 (s, 3H). MS (ESI) m/e 412 (C21H18FN3O3S+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. customThe crude product was purified

出典と根拠

ORDレコード
ord-f7a9808308ae4d899d933a1d8056c773
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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