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

HRID 1776868노트

반응식

HRID 1776868 반응식
[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

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 6344Dichloromethane용매HCID 24386Thionyl Chloride용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0ce6b70d7dc34175b0063aea7b707bca
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09265773B2

반응 노트

불러오는 중…