Dichloromethane → tert-butyl (S)-5-(3-(2-((tert-butoxycarbonyl)amino)-3-oxo-3-(piperidin-1-yl)propyl)phenyl)pent-4-ynoate

HRID 1482251

반응식

HRID 1482251 반응식
I[C:2]1[CH:3]=[C:4]([CH2:8][C@H:9]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:10](=[O:17])[N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:5]=[CH:6][CH:7]=1.[C:26]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])(=[O:31])[CH2:27][CH2:28][C:29]#[CH:30].C(N(CC)CC)C.C(Cl)Cl>CN(C=O)C.CCCCCC.C(OCC)(=O)C.[Cu]I.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:21]([O:20][C:19]([NH:18][C@H:9]([C:10](=[O:17])[N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[CH2:8][C:4]1[CH:3]=[C:2]([C:30]#[C:29][CH2:28][CH2:27][C:26]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH:7]=[CH:6][CH:5]=1)=[O:25])([CH3:24])([CH3:23])[CH3:22]

참가 물질

9

반응물 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 108773414-Pentynoic acid, 1,1-dimethylethyl esterHCID 89668584tert-Butyl (S)-(3-(3-iodophenyl)-1-oxo-1-(piperidin-1-yl)propan-2-yl)carbamate

생성물 1

HCID 89668397tert-butyl (S)-5-(3-(2-((tert-butoxycarbonyl)amino)-3-oxo-3-(piperidin-1-yl)propyl)phenyl)pent-4-ynoate수율 92%

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 6228Dimethylformamide용매HCID 21226206Ethyl acetate hexane용매

실험 절차

tert-Butyl (S)-(3-(3-iodophenyl)-1-oxo-1-(piperidin-1-yl)propan-2-yl)carbamate (Compound SP418, Boc-Phe(3-I)-pip) (5.00 g, 10.91 mmol), tert-butyl pent-4-ynoate (3.36 g, 21.82 mmol) and triethylamine (4.56 ml, 32.7 mmol) were dissolved in DMF (50.0 ml), CuI (0.104 g, 0.545 mmol) and Pd(dppf)Cl2.CH2Cl2 (0.449 g, 0.545 mmol) were added and the mixture was stirred at room temperature for 5 hours. The reaction solution was diluted with hexane/ethyl acetate (1/1) and washed with a saturated aqueous ammonium chloride solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and then filtered and concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0-60:40) to afford the title compound (Compound SP430) (4.84 g, 92%).

후처리

  1. washwashed with a saturated aqueous ammonium chloride solution and brine
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0-60:40)

출처 및 근거

ORD 기록
ord-9e302d7ad16f48638b88abfe84ec7c12
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409952B2

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