tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-methyl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate → 3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-(1-methyl-3-(piperidin-4-yl)-1H-1,2,4-triazol-5-yl)pyrazin-2-amine

HRID 1749670Notes

Reaction equation

HRID 1749670 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:17]2[N:21]([CH3:22])[N:20]=[C:19]([CH:23]3[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24]3)[N:18]=2)=[N:6][C:7]=1[C:8]1[O:9][C:10]([C:13]([CH3:16])([CH3:15])[CH3:14])=[N:11][N:12]=1>C(O)(C(F)(F)F)=O.C(Cl)Cl>[C:13]([C:10]1[O:9][C:8]([C:7]2[C:2]([NH2:1])=[N:3][CH:4]=[C:5]([C:17]3[N:21]([CH3:22])[N:20]=[C:19]([CH:23]4[CH2:24][CH2:25][NH:26][CH2:27][CH2:28]4)[N:18]=3)[N:6]=2)=[N:12][N:11]=1)([CH3:16])([CH3:14])[CH3:15]

Participants

4

Reactant 1

HCID 86727657tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-methyl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate

Product 1

HCID 867276583-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-(1-methyl-3-(piperidin-4-yl)-1H-1,2,4-triazol-5-yl)pyrazin-2-amineYield 86%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-methyl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate (3 g, 6.20 mmol) in TFA (15 mL) and CH2Cl2 (15 mL) was stirred at 25° C. for 1 hour. The mixture was azeotroped with toluene, a 7N solution of ammonia in methanol and dichloromethane were added and the mixture was adsorbed on silica gel. The crude product was purified by flash chromatography on silica gel eluting with 0 to 8% methanol in dichloromethane followed by 0 to 10% methanolic ammonia in dichloromethane. The solvent was evaporated to dryness to afford 3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-(1-methyl-3-(piperidin-4-yl)-1H-1,2,4-triazol-5-yl)pyrazin-2-amine (2.040 g, 86%) as a yellow crystalline solid: 1H NMR Spectrum: (DMSO-d6) 1.45 (9H, s), 1.55-1.66 (2H, m), 1.86 (2H, dd), 2.52-2.61 (2H, m), 2.69-2.78 (1H, m), 2.95-3.02 (2H, m), 4.20 (3H, s), 8.86 (1H, s); Mass Spectrum [M+H]+=384.

Workup

  1. customThe mixture was azeotroped with toluene
  2. additiona 7N solution of ammonia in methanol and dichloromethane were added
  3. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 8% methanol in dichloromethane
  4. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-6f52a52772cb40f094615f2afaa1509f
Source dataset
uspto-grants-2015_10
Patent number
US09156831B2

Reaction notes

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