4-Pyridinemethanamine → 2-methyl-N-(pyridin-4-ylmethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-6-amine

HRID 717797Notes

Reaction equation

Cl[C:2]1[C:10]2[NH:9][C:8]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[Na+].[N:22]1[CH:27]=[CH:26][C:25]([CH2:28][NH2:29])=[CH:24][CH:23]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:15][N:13]1[CH2:12][CH2:11][C:8]2[NH:9][C:10]3[C:6]([C:7]=2[CH2:14]1)=[CH:5][CH:4]=[CH:3][C:2]=3[NH:29][CH2:28][C:25]1[CH:26]=[CH:27][N:22]=[CH:23][CH:24]=1

Participants

Conditions

Temperature: 85 °C

Procedure

6-Chloro-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole (0.5 g, 2.27 mmol), sodium tert-butoxide (1.30 g, 1.36 mmol), palladium acetate (0.101 g, 0.453 mmol) and 2-di-tert-butyl-phosphino-2′-4′-6′-triisopropyl-biphenyl (0.192 g, 0.45 mmol) were mixed in a reaction bottle which was evacuated and back filled with nitrogen for 5 min. Dry toluene (3 mL) was added under a nitrogen atmosphere. (Pyridin-4-yl)methanamine (291 mg, 2.72 mmol) was added and the mixture was heated at 85° C. overnight. The reaction mass was filtered and washed with EtOAc (2×25 mL). The filtrate was concentrated under vacuum and the residue purified on neutral alumina using 0-10% MeOH:EtOAc as eluent. Yield: 180 mg (freebase).

Workup

customwas evacuated
additionback filled with nitrogen for 5 min
additionDry toluene (3 mL) was added under a nitrogen atmosphere
filtrationThe reaction mass was filtered
washwashed with EtOAc (2×25 mL)
concentrationThe filtrate was concentrated under vacuum
customthe residue purified on neutral alumina using 0-10% MeOH

Sources & evidence

ORD record: ord-5140ec2d6f9742339c28c217157f3989
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193728B2

Reaction notes

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