Potassium Carbonate → 5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[3'-(phenylcarbonyl)-4-biphenylyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 2405374ノート

反応式

HRID 2405374 の反応式
[CH:1]1([C:4]([N:6]2[CH2:10][CH2:9][C@@H:8]([CH2:11][C:12]3[N:13]([C:18]4[CH:23]=[CH:22][C:21](B5OC(C)(C)C(C)(C)O5)=[CH:20][CH:19]=4)[C:14](=[O:17])[NH:15][N:16]=3)[CH2:7]2)=[O:5])[CH2:3][CH2:2]1.Br[C:34]1[CH:35]=[C:36]([CH:45]=[CH:46][CH:47]=1)[C:37]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:38].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C(OCC)(=O)C>[CH:1]1([C:4]([N:6]2[CH2:10][CH2:9][C@@H:8]([CH2:11][C:12]3[N:13]([C:18]4[CH:19]=[CH:20][C:21]([C:43]5[CH:42]=[CH:41][CH:40]=[C:39]([C:37]([C:36]6[CH:45]=[CH:46][CH:47]=[CH:34][CH:35]=6)=[O:38])[CH:44]=5)=[CH:22][CH:23]=4)[C:14](=[O:17])[NH:15][N:16]=3)[CH2:7]2)=[O:5])[CH2:3][CH2:2]1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 705483-BromobenzophenoneHCID 673756365-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

生成物 1

HCID 673773895-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[3'-(phenylcarbonyl)-4-biphenylyl]-2,4-dihydro-3H-1,2,4-triazol-3-one収率 55%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

In a sealed tube, a mixture of 5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (179 mg, 0.265 mmol), 3-bromobenzophenone (66 mg, 0.253 mmol), and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (10 mg, 0.012 mmol) in 2M aq potassium carbonate (0.5 mL, 1.00 mmol) and 1,4-dioxane (1.5 mL) was stirred at 100° C. for 1 h. The reaction was cooled to room temperature and the reaction mixture was diluted with ethyl acetate (10 mL). The layers were separated and the aqueous layer was acidified to pH˜5 using 1N aq HCl. The aqueous layer was then extracted with ethyl acetate (20 mL). The organic layers were combined, dried over MgSO4, and concentrated in vacuo. Purification of the residue by silica gel chromatography (0-3% methanol/ethyl acetate) provided the title compound as an ivory solid (68 mg, 55%) after drying in the vacuum oven (70° C.) for 4 days. MS(ES)+ m/e 493.2 [M+H]+.

後処理

  1. temperatureThe reaction was cooled to room temperature
  2. customThe layers were separated
  3. extractionThe aqueous layer was then extracted with ethyl acetate (20 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by silica gel chromatography (0-3% methanol/ethyl acetate)

出典と根拠

ORDレコード
ord-3fb466f983574037a02d260e7b634a17
出典データセット
uspto-grants-2014_08
特許番号
US08802864B2

反応ノート

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