Potassium Phosphate, Tribasic → (3S)-1-[(2S,3S)-2-Amino-3-[4-([1,2,4]triazolo[4,3-alpha]pyridin-6-yl)phenyl]-1-oxobutanyl]-3-fluoropyrrolidine

HRID 1372467노트

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HRID 1372467 반응식
I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[N:9][N:10]=2)[CH:7]=1.C(OC([NH:18][C@@H:19]([C@H:28]([C:30]1[CH:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][CH:31]=1)[CH3:29])[C:20]([N:22]1[CH2:26][CH2:25][C@H:24]([F:27])[CH2:23]1)=[O:21])=O)(C)(C)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.O.C(OCC)(=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[NH2:18][C@@H:19]([C@H:28]([C:30]1[CH:35]=[CH:34][C:33]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([CH:8]=[N:9][N:10]=3)[CH:7]=2)=[CH:32][CH:31]=1)[CH3:29])[C:20]([N:22]1[CH2:26][CH2:25][C@H:24]([F:27])[CH2:23]1)=[O:21]

참가 물질

8

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 69371253Tert-butyl{(1s,2s)-1-{[(3s)-3-fluoropyrrolidin-1-yl]carbonyl}-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propyl}carbamateHCID 693715596-Iodo-[1,2,4]triazolo[4,3-a]pyridine

생성물 1

HCID 10451602(3S)-1-[(2S,3S)-2-Amino-3-[4-([1,2,4]triazolo[4,3-alpha]pyridin-6-yl)phenyl]-1-oxobutanyl]-3-fluoropyrrolidine

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

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온도
90 °C

실험 절차

To a stirred solution of the product (48.0 mg, 0.195 mmol) from Step B in 0.75 mL of ethylene glycol dimethyl ether and 0.75 mL of water was added 62.0 mg (0.13 mmol) of (3S)-1-[(2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-oxobutanyl]-3-fluoropyrrolidine from Example 10, Step B, 1,1′-bis(diphenylphosphino)ferrocene palladium(II) chloride (21.0 mg, 0.26 mmol) and potassium phosphate (83 mg, 0.39 mmol). The reaction mixture was heated at 90° C. for 16 h, and then allowed to cool to room temperature. The mixture was diluted with ethyl acetate, and the solution was washed sequentially with water and saturated aqueous brine, dried (magnesium sulfate), and concentrated under reduced pressure in vacuo to yield the crude coupled product, which was purified by preparative thin layer chromatography (silica gel, 5% methanol/dichloromethane eluant). The resultant product was dissolved in 1 mL of dichloromethane and was treated with 1 mL of trifluoroacetic acid. The reaction was stirred at room temperature for 1 h, and was then concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography (silica gel, 10% methanol/1% ammonium hydroxide/dichloromethane eluant) to afford the title compound. LC/MS 368.2 (M+1).

후처리

  1. temperatureto cool to room temperature
  2. washthe solution was washed sequentially with water and saturated aqueous brine
  3. dry with materialdried (magnesium sulfate)
  4. concentrationconcentrated under reduced pressure in vacuo
  5. customto yield the crude
  6. customwas purified by preparative thin layer chromatography (silica gel, 5% methanol/dichloromethane eluant)
  7. dissolutionThe resultant product was dissolved in 1 mL of dichloromethane
  8. additionwas treated with 1 mL of trifluoroacetic acid
  9. concentrationwas then concentrated under reduced pressure
  10. customThe residue was purified by preparative thin layer chromatography (silica gel, 10% methanol/1% ammonium hydroxide/dichloromethane eluant)

출처 및 근거

ORD 기록
ord-cd374eb264394065945a5ca975db0abd
출처 데이터셋
uspto-grants-2007_01
특허 번호
US07157490B2

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