Trifluoroacetic acid → benzyl 6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-ylcarbamate

HRID 389611Notes

Reaction equation

HRID 389611 reaction equation
[NH:1]([C:3]([C:5]1[N:10]=[C:9]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:8]=[CH:7][CH:6]=1)=O)[NH2:2].[CH:22]1([NH:25][CH:26]=O)[CH2:24][CH2:23]1.C1(N)CC1.FC(F)(F)C(O)=O>C1(C)C=CC=CC=1>[CH:22]1([N:25]2[CH:26]=[N:2][N:1]=[C:3]2[C:5]2[N:10]=[C:9]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:8]=[CH:7][CH:6]=2)[CH2:24][CH2:23]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 69828CyclopropylamineHCID 15475283N-CyclopropylformamideHCID 66848731Benzyl 6-(hydrazinecarbonyl)pyridin-2-ylcarbamate

Product 1

HCID 66851549benzyl 6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-ylcarbamateYield 29.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a sealable flask containing benzyl 6-(hydrazinecarbonyl)pyridin-2-ylcarbamate (1.97 g, 6.89 mmol, 1.0 eq) was added N-cyclopropyl formamide (1.8 mL, 20.7 mmol, 3.0 eq), cyclopropylamine (1.4 mL, 20.7 mmol, 3.0 eq), toluene (0.2 M), and trifluoracetic acid (0.511 mL, 6.89 mmol, 1.0 eq). The flask was sealed and heated to 100° C. for 24 hours. The reaction mixture was concentrated under reduced pressure to provide a yellow oil, which was purified by flash chromatography (Rf=0.44 in 10% methanol/ethyl acetate, gradient flash: 3%→10% methanol in ethyl acetate). The product, which consisted of a mixture of the desired compound with cyclopropyl formamide, was suspended in acetonitrile, sonicated, and the resultant suspension filtered to provide benzyl 6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-ylcarbamate (680 mg).

Workup

  1. customThe flask was sealed
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customto provide a yellow oil, which
  4. customwas purified by flash chromatography (Rf=0.44 in 10% methanol/ethyl acetate, gradient flash: 3%→10% methanol in ethyl acetate)
  5. additionThe product, which consisted of a mixture of the desired compound with cyclopropyl formamide
  6. customsonicated
  7. filtrationthe resultant suspension filtered

Sources & evidence

ORD record
ord-042b9d0d64164e7a9e18c46ce7c1f00f
Source dataset
uspto-grants-2013_02
Patent number
US08378108B2

Reaction notes

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