Morpholine → (2-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-6-yl)(morpholino)methanone

HRID 1776868ノート

反応式

HRID 1776868 の反応式
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:18][CH:17]([C:19](O)=[O:20])[N:8]3[C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([F:16])[C:14]=4[CH:15]=[C:7]3[C:6]=2[N:22]=1.CCN(CC)CC.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>O=S(Cl)Cl.ClCCl.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:18][CH:17]([C:19]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)=[O:20])[N:8]3[C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([F:16])[C:14]=4[CH:15]=[C:7]3[C:6]=2[N:22]=1

参加物

7

反応物 3

HCID 8083MorpholineHCID 8471TriethylamineHCID 867282632-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole-6-carboxylic acid

生成物 1

HCID 86728271(2-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-6-yl)(morpholino)methanone収率 32.9%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 24386Thionyl Chloride溶媒

実験手順

A solution of 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole-6-carboxylic acid (300 mg, 0.94 mmol) in SOCl2 (5 mL) was reflux for 2.0 hours, then concentrated the solution and afforded to the residue. A mixture of the residue, Et3N (0.2 mL) and morpholine (250 mg, 2.87 mmol) in dichloromethane (5 mL) was stirred at room temperature for overnight. Then the mixture was diluted with water (30 mL) and extracted with EtOAc (10 mL*3). The combined organic layer was washed with brine (30 mL), dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using prep-TLC (petroleum ether:EtOAc=1:1) to provide (2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-6-yl)(morpholino)methanone (120 mg, yield: 32.9%). 1H-NMR (CDCl3, 400 MHz) δ7.37˜7.47 (s, 1H), 7.24 (d, J=4.4, 1H), 7.11˜7.20 (m, 2H), 6.94 (d, J=8.4 Hz, 1H), 6.79˜6.86 (m, 1H), 6.70˜6.75 (m, 1H), 3.79˜3.90 (m, 2H), 3.62˜3.73 (m, 3.51˜3.59 (m, 1H), 3.36˜3.45 (m, 1H). MS (M+H)+: 388.

後処理

  1. concentrationconcentrated the solution
  2. customafforded to the residue
  3. extractionextracted with EtOAc (10 mL*3)
  4. washThe combined organic layer was washed with brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified

出典と根拠

ORDレコード
ord-0ce6b70d7dc34175b0063aea7b707bca
出典データセット
uspto-grants-2016_02
特許番号
US09265773B2

反応ノート

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