Ammonium Chloride → 4-(2-(5-(1,3-Dioxan-2-yl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroaniline

HRID 409965Notes

Reaction equation

HRID 409965 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[CH:8]=[CH:9][C:10]([C:13]2[S:21][C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[O:22][C:23]3[CH:28]=[CH:27][C:26]([N+:29]([O-])=O)=[CH:25][C:24]=3[F:32])[CH:14]=2)=[N:11][CH:12]=1.[Cl-].[NH4+]>CCO.O.[Fe]>[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[CH:8]=[CH:9][C:10]([C:13]2[S:21][C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[O:22][C:23]3[CH:28]=[CH:27][C:26]([NH2:29])=[CH:25][C:24]=3[F:32])[CH:14]=2)=[N:11][CH:12]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 252122432-(5-(1,3-Dioxan-2-yl)pyridin-2-yl)-7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridine

Product 1

HCID 579672584-(2-(5-(1,3-Dioxan-2-yl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroanilineYield 103%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a suspension of 318 (10 g, 22.05 mmol) in EtOH (216 ml) and water (108 ml) was added iron powder (10.47 g, 187 mmol) and ammonium chloride (1.015 g, 18.97 mmol). The mixture was heated to reflux for 30 min, filtered while hot and the solids were washed with ether (200 mL). The filtrate and washings were combined and concentrated to afford title compound 319 (9.62 g, 99% yield) as a beige solid. This material was used in the next step (Scheme 18) without additional purification. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.64 (d, J=2.0 Hz, 1H), 8.51 (dd, J=5.6, 2.0 Hz, 1H), 8.34 (s, 1H), 8.28 (dd, J=8.0, 0.8 Hz, 1H), 7.93 (dd, J=8.4, 2.0 Hz, 1H), 7.13 (t, J=9.0 Hz, 1H), 6.61 (dd, J=5.4, 0.6 Hz, 1H), 6.54 (dd, J=13.2, 2.4 Hz, 1H), 6.46 (ddd, J=8.8, 2.8, 0.6 Hz, 1H), 5.67 (s, 1H), 5.56 (s, 2H), 4.19 (dd, J=10.6, 5.0 Hz, 2H), 3.98 (td, J=12.0, 2.5 Hz, 2H), 2.09-1.99 (m, 1H), 1.49 (dt, J=13.2, 1.3 Hz, 1H). MS (m/z): 424.1 (M+H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 30 min
  3. filtrationfiltered while hot and the solids
  4. washwere washed with ether (200 mL)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-b913313c40954a62a40431bff0599b97
Source dataset
uspto-grants-2014_06
Patent number
US08759522B2

Reaction notes

Loading…