Diisopropylethylamine → N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-6-azaspiro[2.5]octane-6-carboxamide

142.3 mg of 1-aminocyclopropanecarbonitrile hydrochloride (1.2 mmol, 1.0 eq.), 163.3 mg of HOAt (1.0 eq.), 0.61 ml of DIPEA (3 eq.) and 456 mg of HATU (1.0 eq.) were added successively to a solution of 348.0 mg of (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoropentanoic acid (1.2 mmol) in 5 ml of DMF. The reaction mixture was stirred at RT for 24 h and then concentrated under reduced pressure. The residue was taken up in 10 ml of dichloromethane, washed with a little sat. NaHCO3 solution and then a little dilute HCl solution (pH=5), and dried over MgSO4. The residue thus obtained was purified by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA). The product-containing fractions were combined and freeze-dried. In this way, N—[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-6-azaspiro[2.5]octane-6-carboxamide was obtained as a colorless amorphous solid.

1. concentrationconcentrated under reduced pressure
2. washwashed with a little sat. NaHCO3 solution
3. dry with materiala little dilute HCl solution (pH=5), and dried over MgSO4
4. customThe residue thus obtained
5. customwas purified by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA)
6. customfreeze-dried

ORD record

ord-de386b5a3d2a4421b07607c1fddb5acd

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609681B2