Potassium Carbonate → 3,10-Difluoro-13,14-bis-pyrrolidin-2-ylmethyl-6,7-dihydro-pyrazino[1,2-a;4,3-a']diindole

HRID 455971Notes

Reaction equation

HRID 455971 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:35][CH:36]3[CH2:40][CH2:39][CH2:38][N:37]3C(=O)C(F)(F)F)=[C:7]3[C:14]4=[C:15]([CH2:23][CH:24]5[CH2:28][CH2:27][CH2:26][N:25]5C(=O)C(F)(F)F)[C:16]5[CH:17]=[CH:18][C:19]([F:22])=[CH:20][C:21]=5[N:13]4[CH2:12][CH2:11][N:8]32)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+]>CO.CCOC(C)=O.O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:35][CH:36]3[CH2:40][CH2:39][CH2:38][NH:37]3)=[C:7]3[C:14]4=[C:15]([CH2:23][CH:24]5[CH2:28][CH2:27][CH2:26][NH:25]5)[C:16]5[CH:17]=[CH:18][C:19]([F:22])=[CH:20][C:21]=5[N:13]4[CH2:12][CH2:11][N:8]32)=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 11430Potassium CarbonateHCID 765717721-(2-(3,10-Difluoro-14-[1-(2,2,2-trifluoro-acetyl)-pyrrolidin-2-ylmethyl]-6,7-dihydro-pyrazino[1,2-a;4,3-a']diindol-13-ylmethyl}-pyrrolidin-1-yl)-2,2,2-trifluoro-ethanone

Product 1

HCID 765717633,10-Difluoro-13,14-bis-pyrrolidin-2-ylmethyl-6,7-dihydro-pyrazino[1,2-a;4,3-a']diindole

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture containing 28 (1.94 g, 2.97 mmol) and K2CO3 (2.05 g, 14.8 mmol) in MeOH (60 mL) was heated at 60° C. for 1.5 h. The reaction mixture was cooled to ambient temperature and diluted with EtOAc and water. The layers were separated and the aqueous phase was extracted three times with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 1.57 g (quant.) of 29 as a yellow solid which was used without further purification. TLC analysis, 1:1 hexane/EtOAc, Rf(28)=0.9; Rf(29)=0.01. 1H NMR (CDCl3, 300 MHz) δ7.65 (m, 1H), 6.98 (app d, J=8.2 Hz, 1H), 6.90 (app t, J=8.3 Hz, 1H), 4.31 (s, 2H), 3.97 (br s, 3H), 3.54 (m, 1H), 3.31 (m, 1H), 3.14 (m, 1H), 2.97 (m, 1H), 1.83 (m, 1H), 1.68 (m, 2H), 1.42 (m, 1H) ppm. 13C NMR (CDCl3, 75 MHz) δ160.6 (d, JC-F=238.7 Hz), 136.2 (d, JC-F=12.0 Hz), 127.1, 125.4, 120.8 (d, JC-F=10.2 Hz), 109.8, 108.9 (d, JC-F=24.6 Hz), 95.3 (d, JC-F=26.3 Hz), 59.6, 45.6, 41.6, 31.0, 30.7, 24.5 ppm.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted three times with EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-a8c55eabdec14d1384c13a117b4cd176
Source dataset
uspto-grants-2013_07
Patent number
US08497297B2

Reaction notes

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