Butylamine → HCID 59455028, compound

HRID 1400576Notes

Reaction equation

HRID 1400576 reaction equation
C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.Cl[C:23]1[CH:31]=[CH:30][C:29]2[N:28]([CH:32]=[C:33]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[CH3:34])[C:27]3[CH2:42][CH2:43][N:44]([CH3:46])[CH2:45][C:26]=3[C:25]=2[CH:24]=1.CC(C)([O-])C.[Na+].[CH2:53]([NH2:57])[CH2:54][CH2:55][CH3:56]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>[CH2:53]([NH:57][C:23]1[CH:31]=[CH:30][C:29]2[N:28](/[CH:32]=[C:33](/[C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)\[CH3:34])[C:27]3[CH2:42][CH2:43][N:44]([CH3:46])[CH2:45][C:26]=3[C:25]=2[CH:24]=1)[CH2:54][CH2:55][CH3:56]

Participants

7

Reactant 4

HCID 8007ButylamineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 67309559HCID 67309559, compound

Product 1

HCID 59455028HCID 59455028, compoundYield 19.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 86644771HCID 86644771, compoundCatalyst

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-5-(2-(4-fluorophenyl)prop-1-enyl)-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole (50 mg, 0.282 mmol), Sodium tert-butoxide (81.2 mg, 0.846 mmol), and palladacycle [palladium (II)acetate+2-(di-t-butylphosphino)biphenyl) (10.7 mg, 0.0282 mmol)] were charged in a reaction bottle which was evacuated and back filled with nitrogen for 5 min. Dry toluene (1 mL) was added under nitrogen atmosphere. Finally, butylamine (14.43 mg, 0.197 mmol) was added and the contents heated at 100° C. overnight. The reaction mixture was filtered and the precipitate washed with EtOAc (2×25 mL). The filtrate was concentrated under vacuum and purified by reverse phase chromatography to yield 15 mg of free base. 1H NMR (CD3OD, free base) δ (ppm): 7.60 (m, 2H), 7.12 (t, 2H), 6.96 (d, 1H), 6.90 (s, 1H), 6.72 (s, 1H), 6.68 (d, 1H), 3.76 (s, 2H), 3.10 (t, 2H), 2.95 (m, 2H), 2.84 (m, 2H), 2.60 (s, 3H), 1.96 (s, 3H), 1.82 (q, 2H), 1.45 (q, 2H), 0.95 (t, 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 (1 mL) was added under nitrogen atmosphere
  8. temperaturethe contents heated at 100° C. overnight
  9. filtrationThe reaction mixture was filtered
  10. washthe precipitate washed with EtOAc (2×25 mL)
  11. concentrationThe filtrate was concentrated under vacuum
  12. custompurified by reverse phase chromatography

Sources & evidence

ORD record
ord-97989c81dbf2428dad9195e665aceae0
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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