Lithium Hexamethyldisilazide → 2-(2H-1,2,3-Triazol-2-yl)-N-[(1S,2R)-2-{[5-(trifluoromethyl)pyrazin-2-yl]oxy}cyclopentyl]benzamide

HRID 1750589Notes

Reaction equation

HRID 1750589 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[OH:11][C@@H:12]1[CH2:16][CH2:15][CH2:14][C@@H:13]1[NH:17][C:18](=[O:30])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[N:25]1[N:29]=[CH:28][CH:27]=[N:26]1.Cl[C:32]1[CH:37]=[N:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][N:33]=1>C1COCC1>[N:29]1[N:25]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[C:18]([NH:17][C@H:13]2[CH2:14][CH2:15][CH2:16][C@H:12]2[O:11][C:32]2[CH:37]=[N:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][N:33]=2)=[O:30])[N:26]=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 189876452-Chloro-5-(trifluoromethyl)pyrazineHCID 118308343N-[(1S,2R)-2-Hydroxycyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide2×

Product 1

HCID 1183082052-(2H-1,2,3-Triazol-2-yl)-N-[(1S,2R)-2-{[5-(trifluoromethyl)pyrazin-2-yl]oxy}cyclopentyl]benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

LiHMDS in THF (1.0 M, 0.477 ml, 0.477 mmol) was added to a solution of N-[(1S,2R)-2-hydroxycyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide (Intermediate 10; 0.100 g, 0.37 mmol) in THF (3 ml) at 0° C. under nitrogen. The reaction was stirred at this temperature for 1 hour and then 2-chloro-5-(trifluoromethyl)pyrazine (CAS number 799557-87-2; 0.059 ml, 0.48 mmol) was added. The mixture was allowed to warm to room temperature and stirred for 5 hours. The reaction was then quenched with water (2 ml) and extracted with ethyl acetate (30 ml). The organics were washed with brine (10 ml), dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica, 0-50% ethyl acetate/petrol) to afford the title compound.

Workup

  1. stirringstirred for 5 hours
  2. customThe reaction was then quenched with water (2 ml)
  3. extractionextracted with ethyl acetate (30 ml)
  4. washThe organics were washed with brine (10 ml)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (silica, 0-50% ethyl acetate/petrol)

Sources & evidence

ORD record
ord-8f487996b46848edb81efafb706f5659
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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