Methylamine → HCID 46199894, compound

HRID 1400575Notes

Reaction equation

HRID 1400575 reaction equation
Cl[C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH:11]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[CH3:13])[C:6]3[CH2:21][CH2:22][N:23]([CH3:25])[CH2:24][C:5]=3[C:4]=2[CH:3]=1.CC(C)([O-])C.[Na+].[CH3:32][NH2:33].C1COCC1>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>[F:20][C:17]1[CH:18]=[CH:19][C:14](/[C:12](/[CH3:13])=[CH:11]/[N:7]2[C:8]3[CH:9]=[CH:10][C:2]([NH:33][CH3:32])=[CH:3][C:4]=3[C:5]3[CH2:24][N:23]([CH3:25])[CH2:22][CH2:21][C:6]2=3)=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 23676156Sodium t-butoxideHCID 67309559HCID 67309559, compound

Product 1

HCID 46199894HCID 46199894, compound

Reagents, catalysts & solvents 1

HCID 86644771HCID 86644771, compoundCatalyst

Conditions

Temperature
100 °C

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 mass was passed through basic alumina using 0-30% ether:hexane and triturated with pentane to yield 300 mg of brownish solid. 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)] was 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, 2M methyl amine in THF (0.39 mL, 0.198 mmol) was added and the contents 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 by reverse phase chromatography to yield 10 mg of free base. 1H NMR (DMSO, oxalate salt) δ (ppm): 7.62 (d, 2H), 7.20 (d, 2H), 6.96 (d, 2H), 6.58 (d, 1H), 6.50 (s, 1H), 4.24 (m, 2H), 3.40 (m, 2H), 2.95 (m, 2H), 2.88 (s, 3H), 2.64 (s, 3H), 1.82 (s, 3H).

Workup

  1. customwas evacuated
  2. additionback filled with nitrogen for 5 min
  3. additionDry toluene (1 mL) was added under nitrogen atmosphere
  4. filtrationThe reaction mixture was filtered
  5. washwashed with EtOAc (2×25 mL)
  6. concentrationThe filtrate was concentrated under vacuum
  7. custompurified by reverse phase chromatography

Sources & evidence

ORD record
ord-0c91482407a74545b504edf3e46c5c1d
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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