Triethylamine → 10-(4-fluorophenethyl)-7-chloro-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole

HRID 535865Notes

Reaction equation

HRID 535865 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]1[CH2:11][CH:12]3[N:16]([CH2:17][C:5]2=1)[CH2:15][CH2:14][CH2:13]3.ClC1C=CC2NC3CCN4C(C=3C=2C=1)CCC4.Br[CH2:36][CH2:37][C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=1.C(N(CC)CC)C>CCO.CCOC(C)=O>[F:44][C:41]1[CH:42]=[CH:43][C:38]([CH2:37][CH2:36][N:7]2[C:8]3[C:4](=[CH:3][C:2]([Cl:1])=[CH:10][CH:9]=3)[C:5]3[CH2:17][N:16]4[CH:12]([CH2:11][C:6]2=3)[CH2:13][CH2:14][CH2:15]4)=[CH:39][CH:40]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 5731534-Fluorophenethyl bromideHCID 6743193010-chloro-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indoleHCID 674340267-chloro-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole

Product 1

HCID 5135609810-(4-fluorophenethyl)-7-chloro-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 7-chloro-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole and 10-chloro-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole (non-separable regioisomers, 500 mg, 2.03 mmol, 1 equiv) and 1-(2-bromoethyl)-4-fluorobenzene (577 mg, 2.84 mmol, 1.4 equiv) were heated to 95° C. with triethyl amine (0.85 mL, 6.09 mmol, 3 equiv) in 6 mL of EtOH for 18 h. The mixture was brought to RT followed by dilution with EtOAc (40 mL), washed with water (2×10 mL), then with brine, dried over sodium sulfate and evaporated under reduced pressure. The crude product was purified by column chromatography over 230-400-mesh silica gel using a gradient of MeOH in EtOAc (0 to 50%). The product was further purified by reverse phase HPLC.

Workup

  1. customwas brought to RT
  2. washwashed with water (2×10 mL)
  3. dry with materialwith brine, dried over sodium sulfate
  4. customevaporated under reduced pressure
  5. customThe crude product was purified by column chromatography over 230-400-mesh silica gel using a gradient of MeOH in EtOAc (0 to 50%)
  6. customThe product was further purified by reverse phase HPLC

Sources & evidence

ORD record
ord-179d864c88274c288bedb955f7bc3449
Source dataset
uspto-grants-2014_10
Patent number
US08859561B2

Reaction notes

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