1,10-Phenanthroline → 9-Chloro-6-((3-fluoro-4-methoxyphenyl)ethynyl)-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole

HRID 1045629Notes

Reaction equation

HRID 1045629 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH3:16])[CH2:14][CH2:15][C:5]=3[C:4]=2[CH:3]=1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[C:40]#[C:41][C:42]1[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[C:44]([F:50])[CH:43]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([C:40]#[C:41][C:42]3[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[C:44]([F:50])[CH:43]=3)[C:6]3[CH2:11][CH2:12][N:13]([CH3:16])[CH2:14][CH2:15][C:5]=3[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 13181,10-PhenanthrolineHCID 62657Potassium Phosphate, TribasicHCID 59455074HCID 59455074, compoundHCID 685585079-Chloro-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole

Product 1

HCID 461917509-Chloro-6-((3-fluoro-4-methoxyphenyl)ethynyl)-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

9-chloro-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (100 mg, 0.42 mmol), CuSO4.5H2O (21 mg, 0.085 mmol), 1,10-Phenanthroline (30 mg, 0.17 mmol) and K3PO4 (180 mg, 0.85 mmol) and 4-(bromoethynyl)-2-fluoro-1-methoxybenzene (131 mg, 0.46 mmol) in toluene (5 mL) were charged and flushed with nitrogen. The reaction mixture was heated at 80° C. for 16 h. The reaction was monitored by LCMS. The reaction mixture was filtered through Celite, washed with DCM. The organic layer was concentrated and purified by column chromatography (100-200 mesh size silica gel, 60-80% ethyl acetate in hexane) to get 9-chloro-6-((3-fluoro-4-methoxyphenyl)ethynyl)-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole which was further purified by prep TLC to get 24 mg of product. 1HNMR (CDCl3, freebase) δ (ppm): 7.40 (d, 2H), 7.30 (m, 2H), 7.20 (d, 1H), 6.95 (t, 1H), 3.90 (s, 3H), 3.10 (m, 2H), 2.90 (m, 6H), 2.50 (s, 3H).

Workup

  1. customflushed with nitrogen
  2. filtrationThe reaction mixture was filtered through Celite
  3. washwashed with DCM
  4. concentrationThe organic layer was concentrated
  5. custompurified by column chromatography (100-200 mesh size silica gel, 60-80% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-e0bcd1cbc80942efb7c1ee4a6a6bbea8
Source dataset
uspto-grants-2013_10
Patent number
US08569287B2

Reaction notes

Loading…