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

HRID 1481475Notes

Reaction equation

HRID 1481475 reaction equation
[CH3:1][N:2]1[CH2:15][CH2:14][C:13]2[C:12]3[CH:11]=[C:10]([CH3:16])[CH:9]=[CH:8][C:7]=3[NH:6][C:5]=2[CH2:4][CH2:3]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>[F:50][C:44]1[CH:43]=[C:42]([C:41]#[C:40][N:6]2[C:7]3[CH:8]=[CH:9][C:10]([CH3:16])=[CH:11][C:12]=3[C:13]3[CH2:14][CH2:15][N:2]([CH3:1])[CH2:3][CH2:4][C:5]2=3)[CH:47]=[CH:46][C:45]=1[O:48][CH3:49]

Participants

6

Reactant 4

HCID 13181,10-PhenanthrolineHCID 62657Potassium Phosphate, TribasicHCID 59455074HCID 59455074, compoundHCID 685600921,2,3,4,5,6-Hexahydro-3,9-dimethylazepino[4,5-b]indole

Product 1

HCID 593681516-((3-Fluoro-4-methoxyphenyl)ethynyl)-3,9-dimethyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

3,9-Dimethyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (100 mg, 0.46 mmol), CuSO4.5H2O (23 mg, 0.093 mmol), 1,10-Phenanthroline (33 mg, 0.18 mmol) and K3PO4 (197 mg, 0.93 mmol) and 4-(bromoethynyl)-2-fluoro-1-methoxybenzene (116 mg, 0.51 mmol) in toluene (5 mL) were added 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 6-((3-fluoro-4-methoxyphenyl)ethynyl)-3,9-dimethyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole which was repurified by prep TLC to get 8 mg product as brown solid. 1HNMR (CDCl3, freebase) δ (ppm): 7.40 (d, 1H), 7.22 (m, 3H), 7.10 (d, 1H), 6.95 (t, 1H), 3.90 (s, 3H), 3.15 (m, 2H), 2.90 (m, 6H), 2.50 (s, 3H), 2.42 (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-b20984924fc84e3e86ced9c6fd7dde60
Source dataset
uspto-grants-2016_08
Patent number
US09409910B2

Reaction notes

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