Potassium Carbonate → HCID 67375552、化合物

HRID 525238ノート

反応式

HRID 525238 の反応式
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.[CH3:25][C:26]1[S:27][CH:28]=[C:29]([C:31]2[CH:36]=[CH:35][C:34](B3OC(C)(C)C(C)(C)O3)=[CH:33][CH:32]=2)[N:30]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[CH:21]1([C:19]([N:16]2[CH2:17][CH2:18][C@@H:14]([CH2:13][C:12]3[N:8]([C:5]4[CH:6]=[CH:7][C:2]([C:34]5[CH:35]=[CH:36][C:31]([C:29]6[N:30]=[C:26]([CH3:25])[S:27][CH:28]=6)=[CH:32][CH:33]=5)=[CH:3][CH:4]=4)[C:9](=[O:24])[NH:10][N:11]=3)[CH2:15]2)=[O:20])[CH2:23][CH2:22]1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 185257492-Methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,3-thiazoleHCID 673755254-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

生成物 1

HCID 67375552HCID 67375552、化合物収率 40%

試薬・触媒・溶媒 2

HCID 53485975CID 53485975触媒HCID 312751,4-Dioxane溶媒

実験手順

A solution of 4-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (0.256 mmol) in 1,4-dioxane (1.5 mL) was treated with 2-methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,3-thiazole (0.281 mmol), dichloro[1,1′-bis(diphenylphosphino) ferrocene]palladium (II)-dichloromethane adduct (10 mg) and 2M aq potassium carbonate (0.767 mmol). The reaction mixture was purged with nitrogen, sealed, and irradiated in a microwave at 150° C. for 15 min. The reaction mixture was cooled to room temperature and was diluted with water (50 mL). The aqueous layer was acidified to pH˜4 using 1N aq HCl and was extracted with dichloromethane. The organic layer was dried over sodium sulfate, treated with Si-Thiol (Silicycle, 20 mg), filtered, and concentrated in vacuo. The crude residue was purified by reverse phase HPLC (25-55% acetonitrile w/0.1% TFA/water w/0.1% TFA). The product fractions from the HPLC were combined, adjusted to pH˜5 with the addition of saturated aq sodium bicarbonate, and extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting product was then purified by flash chromatography (3-10% methanol/dichloromethane) to afford the title compound as an amorphous white solid (40%). MS(ES)+ m/e 486.2 [M+H]+.

後処理

  1. customThe reaction mixture was purged with nitrogen
  2. customsealed
  3. customirradiated in a microwave at 150° C. for 15 min
  4. additionwas diluted with water (50 mL)
  5. extractionwas extracted with dichloromethane
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. additiontreated with Si-Thiol (Silicycle, 20 mg)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude residue was purified by reverse phase HPLC (25-55% acetonitrile w/0.1% TFA/water w/0.1% TFA)
  11. additionadjusted to pH˜5 with the addition of saturated aq sodium bicarbonate
  12. extractionextracted with dichloromethane
  13. dry with materialThe organic layer was dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customThe resulting product was then purified by flash chromatography (3-10% methanol/dichloromethane)

出典と根拠

ORDレコード
ord-500a1a69614e4a46b724dc1eb2b6a585
出典データセット
uspto-grants-2016_05
特許番号
US09340529B2

反応ノート

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