1H-1,2,4-Triazole → HCID 178453987, compound

HRID 711950Notes

Reaction equation

HRID 711950 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[N:6][CH:5]=[N:4]1.CS(O[C@H:13]1[CH2:18][CH2:17][C@H:16]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:15][CH2:14]1)(=O)=O>CN(C)C=O>[N:3]1([C@@H:13]2[CH2:14][CH2:15][C@H:16]([NH:19][C:20](=[O:21])[O:22][C:23]([CH3:25])([CH3:24])[CH3:26])[CH2:17][CH2:18]2)[CH:7]=[N:6][CH:5]=[N:4]1

Participants

5

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 24758Sodium hydrideHCID 178418975HCID 178418975, compound

Product 1

HCID 178453987HCID 178453987, compoundYield 86.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60%, 0.034 g, 0.86 mmol) was added portionwise to a solution of 1H-1,2,4-triazole (0.064 g, 0.92 mmol) in N,N-dimethylformamide (2 mL). After stirred for 5 min, trans-4-[(tert-butoxycarbonyl)amino]cyclohexyl methanesulfonate (0.18 g, 0.61 mmol) was added. The resulting mixture was stirred at 65° C. over weekend. The cooled mixture was poured into ice-cold water, extracted with EtOAc. The organic layers were concentrated and purified on silica gel (eluting with 0 to 5% MeOH in EtOAc) to give tert-butyl [cis-4-(1H-1,2,4-triazol-1-yl)cyclohexyl]carbamate (0.14 g, 86%). LCMS calculated for C13H23N4O2 (M+H)+: m/z=267.2. Found: 267.1. This carbamate intermediate was treated with trifluoroacetic acid (0.28 mL, 3.7 mmol) in methylene chloride (1 mL) at room temperature for 1 h and then concentrated to give the desired product as TFA salt. LCMS calculated for C8H15N4 (M+H)+: m/z=167.1. Found: 167.2.

Workup

  1. stirringThe resulting mixture was stirred at 65° C. over weekend
  2. additionThe cooled mixture was poured into ice-cold water
  3. extractionextracted with EtOAc
  4. concentrationThe organic layers were concentrated
  5. custompurified on silica gel (eluting with 0 to 5% MeOH in EtOAc)

Sources & evidence

ORD record
ord-954c4a66948e41489dba3009fc8b593a
Source dataset
uspto-grants-2015_11
Patent number
US09181271B2

Reaction notes

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