Tris(furan-2-yl)phosphane → Tradipitant

HRID 2251999

반응식

HRID 2251999 반응식
[F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=1)[CH2:6][N:7]1[C:11]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)=[C:10]([Sn](CCCC)(CCCC)CCCC)[N:9]=[N:8]1.Br[C:41]1[C:46]([C:47]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[Cl:55])=[O:48])=[CH:45][CH:44]=[CH:43][N:42]=1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:35][C:34]([F:37])([F:36])[C:32]1[CH:31]=[C:5]([CH:4]=[C:3]([C:2]([F:39])([F:1])[F:38])[CH:33]=1)[CH2:6][N:7]1[C:11]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)=[C:10]([C:41]2[C:46]([C:47]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=3[Cl:55])=[O:48])=[CH:45][CH:44]=[CH:43][N:42]=2)[N:9]=[N:8]1

참가 물질

6

반응물 3

HCID 521585Tris(furan-2-yl)phosphaneHCID 85882881(2-Bromopyridin-3-yl)-(2-chlorophenyl)methanoneHCID 866012444-[3-(3,5-bis(trifluoromethyl)benzyl)-5-tributylstannanyl-3H-[1,2,3]triazol-4-yl]-pyridine

생성물 1

HCID 9916461Tradipitant

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매4회

반응 조건

온도
113 °C

실험 절차

Combine 4-[3-(3,5-bistrifluoromethylbenzyl)-5-tributylstannanyl-3H-[1,2,3]triazol-4-yl]-pyridine (489 g, 740 mmol) and toluene (1 L), add (2-bromopyridin-3-yl)-(2-chlorophenyl)-methanone (240 g, 810 mmol) in toluene (500 mL). Next, add tris(dibenzylideneacetone)dipalladium (16.95 g, 18.5 mmol) and toluene (300 mL). Add tri-2-furylphosphine (17.35 g, 74 mmol) in toluene (200 mL) and heat the reaction mixture to reflux (113° C.). Upon completion of the reaction, remove the solvent by rotary evaporation and purify the crude product by flash column chromatography (dichloromethane/ethyl acetate gradient). Treat the material with activated charcoal in ethyl acetate, wash with 5% aqueous trithiocyanuric acid trisodium salt solution, and recrystallize (ethyl acetate/hexane) to give the title compound. MS(IS) 588 (M+1). TLC (3% MeOH/CH2Cl2) Rf=0.17. 1H NMR (400 MHz, CDCl3): 5.46 (s, 2H); 7.19 (m, 5H); 7.36 (dd, 1H, J=4.9, 7.8); 7.45 (s, 2H); 7.59 (m, 1H); 7.83 (s, 1H); 7.93 (dd, 1H, J=1.5, 7.8); 8.56 (dd, 1H, J=1.5, 4.9); 8.70 (d, 2H, J=5.9).

후처리

  1. customUpon completion of the reaction
  2. customremove the solvent
  3. customby rotary evaporation
  4. custompurify the crude product by flash column chromatography (dichloromethane/ethyl acetate gradient)
  5. additionTreat the material with activated charcoal in ethyl acetate
  6. washwash with 5% aqueous trithiocyanuric acid trisodium salt solution
  7. customrecrystallize (ethyl acetate/hexane)

출처 및 근거

ORD 기록
ord-b7cb45baf76c4d0a8d3c4e614ced8461
출처 데이터셋
uspto-grants-2008_01
특허 번호
US07320994B2

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