3-Pyridinemethanamine → N2-(2-Methoxy-benzyl)-4-pyridin-3-yl-N6-pyridin-3-ylmethyl-quinoline-2,6-diamine

HRID 1949023Notes

Reaction equation

Cl[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[O:20][CH3:21])[CH:6]=[C:5]2[C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1.[N:28]1[CH:33]=[CH:32][CH:31]=[C:30]([CH2:34][NH2:35])[CH:29]=1>C1(C)C=CC=CC=1.C(O)(C)(C)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:21][O:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[CH2:13][NH:12][C:7]1[CH:6]=[C:5]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([NH:35][CH2:34][C:30]3[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=3)[CH:3]=2)[N:8]=1

Participants

Conditions

Temperature: 130 °C

Procedure

(6-Chloro-4-pyridin-3-yl-quinolin-2-yl)-(2-methoxy-benzyl)-amine (185 mg, 0.492 mmol) was dissolved in 5 mL toluene and 1 mL tert. butanol. Argon was bubbled through the solution for 2 minutes to remove oxygen. 3-Picolylamine (160 mg, 1.48 mmol), sodium tert.-butylate (95 mg, 0.99 mmol), palladium acetate (6 mg, 0.027 mmol) and 2-dicyclohexyl-phosphino-2′,4′,6′-triisopropylbiphenyl (X-Phos, 23 mg, 0.05 mmol) were added. The reaction mixture was stirred in a sealed tube at 130° C. for 16 h. The solvent was evaporated and the residue purified by flash chromatography on silica gel (dichloromethane/methanol 100:0->90:10 gradient). The title compound was obtained as a yellow foam (105 mg, 47%), MS: m/e=448.3 (M+H+).

Workup

customArgon was bubbled through the solution for 2 minutes
customto remove oxygen
customThe solvent was evaporated
customthe residue purified by flash chromatography on silica gel (dichloromethane/methanol 100:0->90:10 gradient)

Sources & evidence

ORD record: ord-59ff5c1c0c284922b0623e04f115da6c
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399674B2

Reaction notes

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