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

HRID 1776868Notes

Reaction equation

HRID 1776868 reaction equation
[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

Participants

7

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-0ce6b70d7dc34175b0063aea7b707bca
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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