1-Hydroxybenzotriazole → tert-butyl (cyclopropylmethyl)(trans-2-{4-[(1H-pyrazol-4-ylcarbonyl)amino]phenyl}cyclopropyl)carbamate

HRID 922541Notes

Reaction equation

HRID 922541 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[N:11]([CH2:19][CH:20]2[CH2:22][CH2:21]2)[C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=1.[NH:23]1[CH:27]=[C:26]([C:28](O)=[O:29])[CH:25]=[N:24]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>CN(C=O)C>[C:14]([O:13][C:12](=[O:18])[N:11]([CH2:19][CH:20]1[CH2:22][CH2:21]1)[C@@H:9]1[CH2:10][C@H:8]1[C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:28]([C:26]2[CH:27]=[N:23][NH:24][CH:25]=2)=[O:29])=[CH:3][CH:4]=1)([CH3:17])([CH3:16])[CH3:15]

Participants

8

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 3015937Pyrazole-4-carboxylic acidHCID 86729891Tert-butyl [trans-2-(4-aminophenyl)cyclopropyl](cyclopropylmethyl)carbamate

Product 1

HCID 86729907tert-butyl (cyclopropylmethyl)(trans-2-{4-[(1H-pyrazol-4-ylcarbonyl)amino]phenyl}cyclopropyl)carbamateYield 73.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of tert-butyl [trans-2-(4-aminophenyl)cyclopropyl](cyclopropylmethyl)carbamate (75 mg) in DMF (3 mL) was ice-cooled, and 1H-pyrazole-4-carboxylic acid (33.4 mg), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (143 mg), 1-hydroxybenzotriazole (49.4 mg) and diisopropylethylamine (80 mg) were added. The mixture was stirred at room temperature overnight, and saturated aqueous sodium hydrogen carbonate solution was added under ice-cooling. The mixture was extracted with ethyl acetate, and the extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (72 mg).

Workup

  1. temperaturecooled
  2. temperaturecooling
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe extract was washed with water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-c1e13218f9ce423ca14c2886b38fdd79
Source dataset
uspto-grants-2016_03
Patent number
US09278931B2

Reaction notes

Loading…