Potassium Carbonate → Gsk2194069

HRID 525130

Reaktionsgleichung

Reaktionsgleichung von HRID 525130
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][C@@H:14]3[CH2:18][CH2:17][N:16]([C:19]([CH:21]4[CH2:23][CH2:22]4)=[O:20])[CH2:15]3)=[N:11][NH:10][C:9]2=[O:24])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[CH:35][C:36]3[O:40][CH:39]=[CH:38][C:37]=3[CH:41]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1>[O:40]1[C:36]2[CH:35]=[CH:34][C:33]([C:2]3[CH:7]=[CH:6][C:5]([N:8]4[C:12]([CH2:13][C@@H:14]5[CH2:18][CH2:17][N:16]([C:19]([CH:21]6[CH2:23][CH2:22]6)=[O:20])[CH2:15]5)=[N:11][NH:10][C:9]4=[O:24])=[CH:4][CH:3]=3)=[CH:41][C:37]=2[CH:38]=[CH:39]1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 27951905-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuranHCID 673755254-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

Produkt 1

HCID 67376285Gsk2194069Ausbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

In a microwave vial, a mixture of 4-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (322 mg, 0.77 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (208 mg, 0.85 mmol), and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (32 mg, 0.04 mmol) in 2M aq potassium carbonate solution (1.5 mL, 3 mmol) and 1,4-dioxane (3 mL) was stirred at 100° C. for 3 h. The reaction was cooled to room temperature. The layers were separated and an aliquot of the basic potassium carbonate aqueous layer was analyzed by LCMS and showed that desired product was present. The aqueous layer was acidified using 1N aq HCl solution to pH˜6 by pH paper and was extracted with ethyl acetate (2×50 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. Purification of the residue by silica gel chromatography (Analogix IF280, 0-10% MeOH/CH2Cl2, SF15-12 g, 20 min) followed by another purification (100% EtOAc for 10 min and then 0-8% MeOH/CH2Cl2 for 15 min) and finally subsequent purification by silica gel chromatography (Analogix IF280, SF15-4 g, Solvent A=EtOAc; Solvent B=10% MeOH/CH2Cl2; Gradient: 100% A for 10 min then ramped to 100% B over 20 min (i.e. 0-100% of B/A) provided the title product as a pale yellow solid (232 mg, 0.53 mmol, 69%). MS(ES)+ m/e 428.9 [M+H]+.

Aufarbeitung

  1. temperatureThe reaction was cooled to room temperature
  2. customThe layers were separated
  3. extractionwas extracted with ethyl acetate (2×50 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by silica gel chromatography (Analogix IF280, 0-10% MeOH/CH2Cl2, SF15-12 g, 20 min)
  7. customfollowed by another purification (100% EtOAc for 10 min
  8. custom0-8% MeOH/CH2Cl2 for 15 min) and finally subsequent purification by silica gel chromatography (Analogix IF280, SF15-4 g, Solvent A=EtOAc
  9. waitGradient: 100% A for 10 min then ramped to 100% B over 20 min

Quellen und Nachweise

ORD-Eintrag
ord-58d7690ebd5149cb9f490fd0334c3c14
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09340529B2

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