Potassium Phosphate, Tribasic → 7-(2-(4-fluorophenyl)prop-1-enyl)-10-methyl-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole

HRID 1630535Notes

Reaction equation

HRID 1630535 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]4[CH:17]([C:5]=3[C:4]=2[CH:3]=1)[CH2:16][CH2:15][CH2:14]4.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O.Br[CH:35]=[C:36]([C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=1)[CH3:37]>CN(C=O)C>[F:44][C:41]1[CH:42]=[CH:43][C:38]([C:36]([CH3:37])=[CH:35][N:7]2[C:8]3[CH:9]=[CH:10][C:2]([CH3:1])=[CH:3][C:4]=3[C:5]3[CH:17]4[N:13]([CH2:12][CH2:11][C:6]2=3)[CH2:14][CH2:15][CH2:16]4)=[CH:39][CH:40]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 6703672110-methyl-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indoleHCID 86644757(1-Bromoprop-1-en-2-yl)-4-fluorobenzene

Product 1

HCID 674327827-(2-(4-fluorophenyl)prop-1-enyl)-10-methyl-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a degassed solution of 10-methyl-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole (50 mg, 0.22 mmol), potassium phosphate (93 mg, 0.44 mmol), L-proline (2 mg, 0.01 mmol) and Cu(I)iodide (8 mg, 0.04 mmol) in DMF (1 mL) was added 1-(1-bromoprop-1-en-2-yl)-4-fluorobenzene (95 mg, 0.44 mmol). The reaction mixture was stirred at 120° C. for 18 h. The progress of reaction was monitored by TLC and LCMS. The reaction mixture was filtered through Celite. The filtrate was diluted with water (50 mL), extracted with EtOAc (2×50 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by reverse phase HPLC to yield 7-(2-(4-fluorophenyl)prop-1-enyl)-10-methyl-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole. 1H NMR, (CD3OD, TFA salt) δ (ppm): 7.65 (t, 2H), 7.35 (s, 1H), 7.19 (t, 2H), 7.1 (m, 2H), 6.95 (s, 1H), 5.1 (t, 1H), 3.79 (m, 1H), 3.62 (m, 2H), 3.41 (m, 1H), 3.1 (m, 2H), 2.75 (m, 1H), 2.41 (s, 3H), 2.28 (m, 3H), 1.95 (s, 3H). Chiral HPLC provided the enantiomers 194a and 194b.

Workup

  1. customThe progress of reaction
  2. filtrationThe reaction mixture was filtered through Celite
  3. additionThe filtrate was diluted with water (50 mL)
  4. extractionextracted with EtOAc (2×50 mL)
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-e52d3141c5d04affb5c5c45405a07983
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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