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

HRID 579593

반응식

HRID 579593 반응식
[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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 64092,2,2-Trifluoroethanol용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-efb2bf2f327c464fb2fa445745f1da07
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09040703B2

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