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

HRID 1776862Notes

Reaction equation

CS(O[CH2:6][CH:7]1[N:12]2[C:13]3[CH:14]=[CH:15][CH:16]=[C:17]([F:20])[C:18]=3[CH:19]=[C:11]2[C:10]2[N:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:9]=2[O:8]1)(=O)=O.[N-:26]=[N+:27]=[N-:28].[Na+].O>CN(C=O)C>[N:26]([CH2:6][CH:7]1[N:12]2[C:13]3[CH:14]=[CH:15][CH:16]=[C:17]([F:20])[C:18]=3[CH:19]=[C:11]2[C:10]2[N:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:9]=2[O:8]1)=[N+:27]=[N-:28]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of (2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-6-yl)methyl methanesulfonate (5 g, 13.08 mmol) in DMF (50 mL), NaN3 (4.18 g, 39.25 mmol) was added at room temperature. The mixture was stirred at 60° C. for 6 hours under N2 protection. After H2O was added, the mixture was extracted with EtOAc (20 mL*3). The combined organic phases were washed with water and brine, dried over Na2SO4 and concentrated to provide 6-(azidomethyl)-2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (4.2 g, yield: 97.4%). The crude product was used in the next step without purification. 1H-NMR (CDCl3, 400 MHz) δ 3.62˜3.71 (m, 1H), 3.72˜3.81 (m, 1H), 5.28˜5.34 (t, J=5.6 Hz, 1H), 6.76˜6.83 (t, J=4.4 Hz, 1H), 6.92˜7.00 (m, 1H), 7.05˜7.13 (s, 1H), 7.23˜7.31 (m, 1H), 7.39˜7.51 (m, 2H), 7.57˜7.67 (d, J=8.8 Hz, 1H). MS (M+H)+: 330.

Workup

extractionthe mixture was extracted with EtOAc (20 mL*3)
washThe combined organic phases were washed with water and brine
dry with materialdried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-4dbadf72000a498a8a286e50dfb3689b
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09265773B2

Reaction notes

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