Water → 2-Acetylamino-2-(5'-Chloro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-hex-5-enoic acid, tert-butylamide

HRID 579593Notes

Reaction equation

HRID 579593 reaction equation
[C:1]([N+:5]#[C-:6])([CH3:4])([CH3:3])[CH3:2].[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([N:14]2[CH2:19][CH2:18][CH:17]([C:20](=O)[CH2:21][CH2:22][CH:23]=[CH2:24])[CH2:16][CH2:15]2)=[N:12][CH:13]=1.[C:26]([O-:29])(=O)[CH3:27].[NH4+:30].[OH2:31]>FC(F)(F)CO>[C:1]([NH:5][C:6](=[O:31])[C:20]([NH:30][C:26](=[O:29])[CH3:27])([CH:17]1[CH2:18][CH2:19][N:14]([C:11]2[CH:10]=[CH:9][C:8]([Cl:7])=[CH:13][N:12]=2)[CH2:15][CH2:16]1)[CH2:21][CH2:22][CH:23]=[CH2:24])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 23577Tert-Butyl isocyanideHCID 517165Ammonium AcetateHCID 668334951-(5'-chloro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-pent-4-en-1-one

Product 1

HCID 680643072-Acetylamino-2-(5'-Chloro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-hex-5-enoic acid, tert-butylamideYield 74%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Procedure

tert-Butyl isocyanide (538 mg, 0.73 mL, 6.48 mmol) was added to a stirred slurry of 1-(5′-chloro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-pent-4-en-1-one (900 mg, 3.24 mmol) and ammonium acetate (1.0 g, 12.96 mmol) in 2,2,2-trifluoroethanol (0.5 mL). After stirring at room temperature for 5 days, the reaction mixture was poured into water and extracted with ethyl acetate (3×). The combined organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (silica gel, 10-40% ethyl acetate in heptane) gave the title compound as a white solid (1.02 g, 74%); 1H NMR (CDCl3, 300 MHz) δ 8.06 (dd, J1=2.5 Hz, J2=0.5 Hz, 1H), 7.37 (dd, J1=9 Hz, J2=2.5 Hz, 1H), 7.01 (br s, NH, 1H), 6.55 (dd, J1=9.0 Hz, J2=0.5 Hz, 1H), 5.78 (m, 1H), 5.50 (br s, NH, 1H), 4.97 (m, 2H), 4.38 (m, 1H), 4.14 (m, 1H), 3.00 (ddd, J1=14.5 Hz, J2=11.5 Hz, J3=5.0 Hz, 1H), 2.72 (td, J1=13 Hz, J2=2.5 Hz, 2H), 2.44 (tt, J1=2.5 Hz, J2=3 Hz, 1H), 1.97-2.08 (m, 1H), 2.00 (s, 3H), 1.80 (m, 3H), 1.20-1.52 (m, 3H) and 1.30 (s, 9H).

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washThe combined organic phase was washed with saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash column chromatography (silica gel, 10-40% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-efb2bf2f327c464fb2fa445745f1da07
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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