Sodium Bicarbonate → 6-(2-(benzyloxy)ethyl)-2-chloro-11-fluoro-12,12a-dihydro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole

HRID 1776854Notes

Reaction equation

HRID 1776854 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH:11]=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:13][C:14]1[N:19]=[C:18]([CH:20]2[CH2:28][C:27]3[C:22](=[CH:23][CH:24]=[CH:25][C:26]=3[F:29])[NH:21]2)[C:17](O)=[CH:16][CH:15]=1.C([O-])(O)=O.[Na+]>CC#N.C(O)(C(F)(F)F)=O>[CH2:1]([O:8][CH2:9][CH2:10][CH:11]1[N:21]2[C:22]3[CH:23]=[CH:24][CH:25]=[C:26]([F:29])[C:27]=3[CH2:28][CH:20]2[C:18]2[N:19]=[C:14]([Cl:13])[CH:15]=[CH:16][C:17]=2[O:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 108882613-(Benzyloxy)propanalHCID 867262936-Chloro-2-(4-fluoroindolin-2-yl)pyridin-3-ol

Product 1

HCID 867282566-(2-(benzyloxy)ethyl)-2-chloro-11-fluoro-12,12a-dihydro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indoleYield 69.5%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of 3-(benzyloxy)propanal (465 mg, 2.83 mmol) and 6-chloro-2-(4-fluoroindolin-2-yl)pyridin-3-ol (500 mg, 1.89 mmol) in MeCN (15 mL) was added TFA (10 mg, 0.09 mmol). The mixture was stirred at room temperature for 3 hours. The it was basified by NaHCO3 (aq.), and then it was concentrated in vacuo, the resulting residue was purified using column chromatography (petroleum ether:EtOAc=10:1) to provide 6-(2-(benzyloxy)ethyl)-2-chloro-11-fluoro-12,12a-dihydro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (540 mg, yield: 69%). 1H-NMR (CDCl3, 400 MHz) δ 7.28˜7.38 (m, 5H), 7.04˜7.10 (m, 2H), 6.95 (d, J=8.8 Hz, 1H), 6.60 (d, J=8.0 Hz, 1H), 6.50 (t, J=8.0 Hz, 1H), 5.93 (t, J=7.2 Hz, 1H), 5.02 (d, J=8.8 Hz, 1H), 4.55 (d, J=2.4 Hz, 1H), 3.62˜3.71 (m, 3H), 3.40˜3.48 (m, 1H), 2.19˜2.27 (m, 2H). MS (M+H)+: 411.

Workup

  1. concentrationit was concentrated in vacuo
  2. customthe resulting residue was purified

Sources & evidence

ORD record
ord-0075792f960f4373b1a07de9d5730eac
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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