Diisopropylethylamine → tert-Butyl 3-({6-[(tert-butoxycarbonyl)amino]-5-(trifluoroacetyl)pyridin-2-yl}amino)piperidine-1-carboxylate

HRID 1182997Notes

Reaction equation

[NH2:1][CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.Cl[C:16]1[N:21]=[C:20]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:19]([C:30](=[O:35])[C:31]([F:34])([F:33])[F:32])=[CH:18][CH:17]=1.C(N(C(C)C)CC)(C)C>CS(C)=O.C(OCC)(=O)C>[C:25]([O:24][C:23]([NH:22][C:20]1[N:21]=[C:16]([NH:1][CH:2]2[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]2)[CH:17]=[CH:18][C:19]=1[C:30](=[O:35])[C:31]([F:32])([F:33])[F:34])=[O:29])([CH3:28])([CH3:26])[CH3:27]

Participants

Conditions

Temperature: 90 °C

Procedure

561 mg (2.8 mmol) of tert-butyl 3-aminopiperidine-1-carboxylate, 700 mg (2.16 mmol) of tert-butyl [6-chloro-3-(trifluoroacetyl)pyridin-2-yl]carbamate (Example 7A) and 0.56 ml (3.23 mmol) of diisopropylethylamine were suspended in 14 ml of DMSO and heated to 90° C. in a microwave reactor for 45 min. The reaction mixture was diluted with ethyl acetate (100 ml) and washed with saturated aqueous ammonium chloride solution (3×40 ml) and then with saturated aqueous sodium hydrogencarbonate solution (40 ml). The organic phase was dried over magnesium sulphate and concentrated. The residue was chromatographed on silica gel (eluent: cyclohexane/ethyl acetate 5:1 to 1:1). 670 mg (63% of theory) of the product were isolated.

Workup

washwashed with saturated aqueous ammonium chloride solution (3×40 ml)
dry with materialThe organic phase was dried over magnesium sulphate
concentrationconcentrated
customThe residue was chromatographed on silica gel (eluent: cyclohexane/ethyl acetate 5:1 to 1:1)
custom670 mg (63% of theory) of the product were isolated

Sources & evidence

ORD record: ord-6f7ab84fe7234ff6b4d6468ab81c1f44
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08664246B2

Reaction notes

Loading…