Dimethylformamide → HCID 59355588, compound

HRID 913081Notes

Reaction equation

HRID 913081 reaction equation
Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=1.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([NH2:23])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+]>C(N(C(C)C)C(C)C)C>[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([NH:23][C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=2)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:11])[CH3:12]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 12682914-Amino-1-Boc-piperidineHCID 51520946-Chloro-3-pyridinecarbonitrile

Product 1

HCID 59355588HCID 59355588, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 81531DiisopropylethylamineSolvent

Procedure

A mixture of 6-chloro-nicotinonitrile (2.1 g, 15.16 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (4.86 g, 24.25 mmol, 1.6 equiv; commercially available) in N-ethyl diisopropylamine (5 mL) and anhydrous DMF (10 mL) was stirred at 60° C. for 3 d. To the reaction mixture was added a sat. solution of Na2CO3 (100 mL) and the crude extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over MgSO4, concentrated by evaporation under reduced pressure and the crude material purified with silica column chromatography eluting with toluene/ethyl acetate (4:1) to provide 2.90 g (63%) of the title compound. 1H NMR (300 MHz, DMSO): δ 1.24-1.42 (m, 2H), 1.41 (s, 9H), 1.84-1.89 (m, 2H), 2.85-2.94 (m, 2H), 3.87-3.91 (m, 2H), 3.98 (br s, 1H), 6.54 (d, J=8.9 Hz, 1H), 7.53 (d, J=7.5 Hz, 1H), 7.66 (dd, J=8.9 Hz, J=2.1 Hz, 1H), 8.38 (d, J=2.1 Hz, 1H), 13C NMR (75 MHz, DMSO): δ 828.04, 31.19, 42.25, 47.12, 78.58, 94.49, 108.62, 118.91, 138.53, 153.00, 153.89, 159.17. MS (ISP): 303.1 [M+H]+.

Workup

  1. extractionthe crude extracted with ethyl acetate (3×100 mL)
  2. dry with materialThe combined organic phases were dried over MgSO4
  3. concentrationconcentrated by evaporation under reduced pressure
  4. customthe crude material purified with silica column chromatography
  5. washeluting with toluene/ethyl acetate (4:1)

Sources & evidence

ORD record
ord-ac9bffc171a84c289d73d4107b8b5ce7
Source dataset
uspto-grants-2011_09
Patent number
US08026255B2

Reaction notes

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