Hydrogen Bromide → 5-Cyclobutyl-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid [2-methanesulfonyl-1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide

HRID 1480191Notes

Reaction equation

HRID 1480191 reaction equation
[CH:1]1([C:5]2[C:6]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[CH:7][C:8]([C:11]([OH:13])=O)=[N:9][CH:10]=2)[CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH3:51][C:52]1[O:56][N:55]=[C:54]([C:57]([NH2:64])([CH3:63])[CH2:58][S:59]([CH3:62])(=[O:61])=[O:60])[N:53]=1.Br>CN(C=O)C>[CH:1]1([C:5]2[C:6]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[CH:7][C:8]([C:11]([NH:64][C:57]([CH3:63])([C:54]3[N:53]=[C:52]([CH3:51])[O:56][N:55]=3)[CH2:58][S:59]([CH3:62])(=[O:61])=[O:60])=[O:13])=[N:9][CH:10]=2)[CH2:2][CH2:3][CH2:4]1

Participants

7

Reactant 5

HCID 260Hydrogen BromideHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 902034302-(5-Methyl-1,2,4-oxadiazol-3-yl)-1-methylsulfonyl-propan-2-amineHCID 902048685-Cyclobutyl-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid

Product 1

HCID 762847535-Cyclobutyl-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid [2-methanesulfonyl-1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amideYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-Cyclobutyl-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (example 108f, 40 mg, 145 μmol) in dry DMF (1.00 ml) was added DIEA (76.2 μl, 436 μmol) and TBTU (49.0 mg, 153 μmol) and the reaction mixture was stirred at room temperature for 20 minutes. Addition of 2-(5-methyl-1,2,4-oxadiazol-3-yl)-1-methylsulfonyl-propan-2-amine;hydrobromide (enantiomer B) (example 125b, 45.8 mg, 153 μmol) to the reaction mixture and the latter was stirred at room temperature for 2 hours. The crude was directly purified by preparative HPLC without any work-up to yield the title compound (20 mg, 29%); MS (ESI, m/z): 477.5 (M+H+).

Workup

  1. customThe crude was directly purified by preparative HPLC without any work-up

Sources & evidence

ORD record
ord-d26de9262d73487ba08c6ec7b00251f9
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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