1-Methylpiperazine → HCID 59455111, compound

HRID 1401648Notes

Reaction equation

HRID 1401648 reaction equation
[C:1](P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.ClC1[CH:31]=[CH:30][C:29]2[N:28]([CH:32]=[C:33]([C:35]3[CH:40]=[CH:39][N:38]=[CH:37][CH:36]=3)[CH3:34])[C:27]3[CH2:41][CH2:42][N:43]([CH3:45])[CH2:44][C:26]=3[C:25]=2[CH:24]=1.CC(C)([O-])C.[Na+].[CH3:52][N:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:45][N:43]1[CH2:42][CH2:41][C:27]2[N:28](/[CH:32]=[C:33](/[C:35]3[CH:36]=[CH:37][N:38]=[CH:39][CH:40]=3)\[CH3:34])[C:29]3[CH:30]=[CH:31][C:52]([N:53]4[CH2:58][CH2:57][N:56]([CH3:1])[CH2:55][CH2:54]4)=[CH:24][C:25]=3[C:26]=2[CH2:44]1

Participants

6

Reactant 4

HCID 531671-MethylpiperazineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 67309592HCID 67309592, compound

Product 1

HCID 59455111HCID 59455111, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

Palladium (II) acetate (314 mg, 1.4 mmol) and 2-(di-t-butylphosphino)biphenyl (418 mg, 1.4 mmol) were charged in a reaction bottle which was evacuated and backfilled with nitrogen. Toluene (10 mL) was added dropwise under nitrogen and stirred at RT overnight. The reaction mixture was passed through basic alumina using 0-30% ether:hexane and triturated with pentane to get brownish solid. Yield: 300 mg. 8-chloro-2,3,4,5-tetrahydro-2-methyl-5-(2-(pyridin-4-yl)prop-1-enyl)-1H-pyrido[4,3-b]indole (100 mg, 0.29 mmol), Sodium tert-butoxide (134 mg, 1.45 mmol), palladacycle (palladium (II)acetate+2-(di-t-butylphosphino)biphenyl) (26 mg, 0.058 mmol) was charged in a reaction bottle which was evacuated and back filled with nitrogen for 5 min. and dry toluene (2 mL) was added under nitrogen atmosphere. 1-Methylpiperazine (37 mg, 0.37 mmol) was added and heated at 100° C. overnight. The reaction mixture was filtered and washed with EtOAc (2×25 mL). The filtrate was concentrated under vacuum and purified on reverse phase chromatography. Yield: 30 mg. 1H NMR (CDCl3, free base) δ (ppm): 8.50 (d, 2H), 7.50 (d, 2H), 7.16 (s, 1H), 7.05 (d, 1H), 6.95 (m, 2H), 3.78 (s, 2H), 3.20 (m, 4H), 2.92 (m, 2H), 2.82 (m, 2H), 2.74 (m, 4H), 2.60 (s, 3H), 2.40 (s, 3H), 2.0 (s, 3H).

Workup

  1. customwas evacuated
  2. additionToluene (10 mL) was added dropwise under nitrogen
  3. customhexane and triturated with pentane
  4. customto get brownish solid
  5. customwas evacuated
  6. additionback filled with nitrogen for 5 min.
  7. additiondry toluene (2 mL) was added under nitrogen atmosphere
  8. temperatureheated at 100° C. overnight
  9. filtrationThe reaction mixture was filtered
  10. washwashed with EtOAc (2×25 mL)
  11. concentrationThe filtrate was concentrated under vacuum
  12. custompurified on reverse phase chromatography

Sources & evidence

ORD record
ord-237ebb772d1f4a6a8fabce31f68e4457
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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