HOAt → tert-Butyl [(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]carbamate
Reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]([F:17])([F:16])[CH3:15])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:18]1C=[N:22][C:21]2N(O)N=[N:26][C:20]=2[CH:19]=1.CCN=C=NCCCN(C)C.Cl>ClCCl>[C:21]([C:20]1([NH:26][C:10]([C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:13][C:14]([F:17])([F:16])[CH3:15])=[O:12])[CH2:19][CH2:18]1)#[N:22]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
1.35 g (5.33 mmol) of the product from example 16, 810 mg (6.83 mmol, 1.3 eq.) of 1-amino-1-cyclopropylnitrile hydrochloride and 943 mg (6.93 mmol, 1.3 eq.) of HOAt were dissolved or suspended in 18 ml of dichloromethane, cooled to 0° C. and then admixed with 1.33 g (6.93 mmol, 1.3 eq.) of EDCl and 1.76 ml (1.596 g, 13.86 mmol, 2.6 eq.) of NEM. The mixture was stirred at 0° C. to RT for 16 h. The reaction mixture was then diluted with 40 ml of DCM and extracted by shaking with 1 N HCl solution, saturated sodium hydrogencarbonate solution and saturated NaCl solution. The organic phase was dried over sodium sulfate and concentrated by evaporation under reduced pressure. The product was sufficiently clean for further reactions.
Workup
- extractionextracted
- stirringby shaking with 1 N HCl solution, saturated sodium hydrogencarbonate solution and saturated NaCl solution
- dry with materialThe organic phase was dried over sodium sulfate
- concentrationconcentrated by evaporation under reduced pressure
Sources & evidence
- ORD record
- ord-57572040f5314aa98d868eef6e0da799
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08609681B2
Reaction notes
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