6-Methoxy-3-pyridinylamine → N-(6-Methoxypyridin-3-YL)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-YL)-9H-purin-6-YL)quinolin-2-amine

HRID 1621497Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.Cl[C:11]1[C:20]([C:21]2[N:29]=[C:28]([CH3:30])[N:27]=[C:26]3[C:22]=2[N:23]=[CH:24][N:25]3[CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][O:32]2)=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>O1CCOCC1>[CH3:9][O:8][C:5]1[N:6]=[CH:7][C:2]([NH:1][C:11]2[C:20]([C:21]3[N:29]=[C:28]([CH3:30])[N:27]=[C:26]4[C:22]=3[N:23]=[CH:24][N:25]4[CH:31]3[CH2:36][CH2:35][CH2:34][CH2:33][O:32]3)=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=2)=[CH:3][CH:4]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 5-amino-2-methoxypyridine (50 mg, 0.41 mmol, Aldrich, St. Louis, Mo.) and 2-chloro-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)quinoline (77 mg, 0.20 mmol) in dioxane (4 mL) at 0° C. was treated with LiHMDS (1 M in THF, 0.51 mL, 0.51 mmol). The reaction mixture was stirred at 0° C. for 1 h and 18 h at room temperature. Then an additional amount of LiHMDS (1 M in THF, 0.51 mL, 0.51 mmol) was added and the reaction mixture stirred at room temperature for 2 h. The reaction was quenched by the addition of MeOH (2 mL) and the solvents were removed under vacuum. Purification of the crude reaction mixture by silica gel chromatography (2 to 3% MeOH/CH2Cl2) provided the title compound as a dark orange solid. m/z (ESI, +ve ion) 468 (M+H)+.

Workup

stirringthe reaction mixture stirred at room temperature for 2 h
customThe reaction was quenched by the addition of MeOH (2 mL)
customthe solvents were removed under vacuum
customPurification of the crude
customreaction mixture by silica gel chromatography (2 to 3% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-3aede9fa549c441ca4bedb0bfe614791
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772480B2

Reaction notes

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