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

HRID 2088658Notes

Reaction equation

HRID 2088658 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.[C:15]([O:19][C:20](=[O:35])[NH:21][C:22]1[C:27]([C:28](=[O:33])[C:29]([F:32])([F:31])[F:30])=[CH:26][CH:25]=[C:24](Cl)[N:23]=1)([CH3:18])([CH3:17])[CH3:16].C(N(C(C)C)CC)(C)C>CS(C)=O.C(OCC)(=O)C>[C:15]([O:19][C:20]([NH:21][C:22]1[N:23]=[C:24]([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:25]=[CH:26][C:27]=1[C:28](=[O:33])[C:29]([F:30])([F:31])[F:32])=[O:35])([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 5458091-BOC-3-AminopiperidineHCID 57911758tert-Butyl[6-chloro-3-(trifluoroacetyl)pyridin-2-yl]carbamate

Product 1

HCID 57911775tert-Butyl 3-({6-[(tert-butoxycarbonyl)amino]-5-(trifluoroacetyl)pyridin-2-yl}amino)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

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 11A) and 0.56 ml (3.23 mmol) of diisopropylethylamine were suspended in 14 ml of DMSO and heated in a microwave reactor at 90° C. 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 bicarbonate solution (40 ml), and the organic phase was dried over magnesium sulfate, diluted and concentrated. The residue was chromatographed on silica gel (mobile phase: cyclohexane-ethyl acetate 5:1 to 1:1). This gave 670 mg (63% of theory) of the product.

Workup

  1. washwashed with saturated aqueous ammonium chloride solution (3×40 ml)
  2. dry with materialwith saturated aqueous sodium bicarbonate solution (40 ml), and the organic phase was dried over magnesium sulfate
  3. additiondiluted
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel (mobile phase: cyclohexane-ethyl acetate 5:1 to 1:1)

Sources & evidence

ORD record
ord-0a3993ae6d9c406b879b06bfaac5b7fc
Source dataset
uspto-grants-2013_05
Patent number
US08436003B2

Reaction notes

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