Azidotrimethylsilane → ((2S,3R)-3-Methyl-2-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)piperidin-1-yl)(5-methyl-2-(2H-tetrazol-5-yl)phenyl)methanone

HRID 60928Notes

Reaction equation

[CH3:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([N:12]2[CH2:17][CH2:16][CH2:15][C@@H:14]([CH3:18])[C@H:13]2[CH2:19][NH:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][N:22]=2)=[O:11])[CH:3]=1.[Si]([N:35]=[N+:36]=[N-:37])(C)(C)C>C1(C)C=CC=CC=1>[CH3:18][C@@H:14]1[CH2:15][CH2:16][CH2:17][N:12]([C:10]([C:4]2[CH:3]=[C:2]([CH3:1])[CH:9]=[CH:8][C:5]=2[C:6]2[N:35]=[N:36][NH:37][N:7]=2)=[O:11])[C@@H:13]1[CH2:19][NH:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:29])([F:30])[F:28])=[CH:23][N:22]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 4-methyl-2-((2S,3R)-3-methyl-2-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)piperidine-1-carbonyl)benzonitrile (obtained from Example A22, 0.098 g, 0.235 mmol), TMSN3 (0.06 mL, 0.47 mmol) and SnO(n-Bu)2 (0.006 g, 0.024 mmol) in toluene (2 mL) was heated at 110° C. overnight. The mixture was cooled to rt and filtered through a pad of diatomaceous earth, washing with methanol. The solvent was removed in vacuo and the resulting crude residue was purified by reverse-phase preparative HPLC to obtain the title compound. ESI-MS (m/z): 460 [M+1]+.

Workup

temperatureThe mixture was cooled to rt
filtrationfiltered through a pad of diatomaceous earth
washwashing with methanol
customThe solvent was removed in vacuo
customthe resulting crude residue was purified by reverse-phase preparative HPLC

Sources & evidence

ORD record: ord-261b1e03cc1743b5b094fd17590c7c39
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440982B2

Reaction notes

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