Benzyl prop-2-yn-1-ylcarbamate → Benzyl 3-(6-{3-[(tert-butoxycarbonyl)amino]prop-1-ynyl}pyridin-3-yl)prop-2-ynylcarbamate

HRID 49568

반응식

HRID 49568 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]#[C:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[N:6][CH:7]=1.[C:19]([NH:29][CH2:30][C:31]#[CH:32])([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20]>C(NC(C)C)(C)C.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:14]([O:13][C:12]([NH:11][CH2:10][C:9]#[C:8][C:5]1[N:6]=[CH:7][C:2]([C:32]#[C:31][CH2:30][NH:29][C:19](=[O:20])[O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:3][CH:4]=1)=[O:18])([CH3:17])([CH3:16])[CH3:15]

참가 물질

7

반응물 2

HCID 11137906Benzyl prop-2-yn-1-ylcarbamateHCID 21299384tert-Butyl 3-(5-bromopyridin-2-yl)prop-2-ynylcarbamate

생성물 1

HCID 21299383Benzyl 3-(6-{3-[(tert-butoxycarbonyl)amino]prop-1-ynyl}pyridin-3-yl)prop-2-ynylcarbamate수율 55.1%

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 7912Diisopropylamine용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of tert-butyl 3-(5-bromopyridin-2-yl)prop-2-ynylcarbamate (3-1) (1.44 g), N-Cbz propargylamine (1.09 g), Pd(PPh3)2Cl2 (73 mg), and CuI (10 mg) in diisopropylamine (25 mL) was heated under reflux under a nitrogen atmosphere for 3 hours. The mixture was cooled to ambient temperature and diluted with ethyl acetate (70 mL). The precipitates were filtered and rinsed with ethyl acetate (30 mL). The filtrate and washings were combined, concentrated under reduced pressure, and purified by silica gel column chromatography using a mixture of MTBE and hexanes (2:3 to 4:1). The fractions containing the product were combined and concentrated under reduced pressure. The residue was crystallized from MTBE. Crystals were filtered, washed with MTBE, and dried to give 6-1 (1.07 g). An additional 120 mg of 6-1 was isolated from the mother liquors and washings.

후처리

  1. temperaturewas heated
  2. temperatureunder reflux under a nitrogen atmosphere for 3 hours
  3. filtrationThe precipitates were filtered
  4. washrinsed with ethyl acetate (30 mL)
  5. concentrationconcentrated under reduced pressure
  6. custompurified by silica gel column chromatography
  7. additiona mixture of MTBE and hexanes (2:3 to 4:1)
  8. additionThe fractions containing the product
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was crystallized from MTBE
  11. filtrationCrystals were filtered
  12. washwashed with MTBE
  13. customdried

출처 및 근거

ORD 기록
ord-8736816034304086904f1b92f0cec74b
출처 데이터셋
uspto-grants-2004_03
특허 번호
US06706885B2

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