Methanol → 2-chloro-11-fluoro-6-(morpholinomethyl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole

HRID 1776869Notes

Reaction equation

HRID 1776869 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:18][CH:17]([C:19]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=O)[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:27]=1.S(C)C.CO.O>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:18][CH:17]([CH2:19][N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[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:27]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 1068Dimethyl SulfideHCID 86728271(2-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-6-yl)(morpholino)methanone

Product 1

HCID 867282722-chloro-11-fluoro-6-(morpholinomethyl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indoleYield 86.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-6-yl)(morpholino)methanone (60 mg, 0.16 mmol) in THF (2 mL) was added to BH3.SMe2 (1 mL, 1 mmol) at 0° C. After being stirred for overnight, MeOH and water was added, the mixture was extracted with EtOAc (10 mL*3). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using prep-TLC (petroleum ether:EtOAc=2:1) to provide 2-chloro-11-fluoro-6-(morpholinomethyl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (50 mg, yield: 86.2%). 1H-NMR (CDCl3, 400 MHz) δ 7.28˜7.34 (m, 1H), 7.22˜7.26 (m, 1H), 7.13˜7.22 (m, 2H), 7.09 (d, J=8.4, 1H), 6.79˜6.86 (m, 1H), 6.43 (t, J=4.8 Hz, 1H), 3.45˜3.53 (m, 2H), 3.34˜3.43 (m, 2H), 2.80˜2.88 (m, 1H), 2.63˜2.70 (m, 1H), 2.30˜2.39 (m, 2H), 2.21˜2.29 (m, 2H). MS (M+H)+: 374.

Workup

  1. customat 0° C
  2. extractionthe mixture was extracted with EtOAc (10 mL*3)
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified

Sources & evidence

ORD record
ord-518b4b63b87e4e5982a1758c624bad80
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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