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

HRID 525134ノート

反応式

HRID 525134 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.[Cl:25][C:26]1[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:27]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[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:29]5[CH:28]=[CH:27][C:26]([Cl:25])=[CH:31][C:30]=5[Cl:32])=[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

7

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 2734659(2,4-Dichlorophenyl)boronic acidHCID 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 533735535-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-(2',4'-dichloro-4-biphenylyl)-2,4-dihydro-3H-1,2,4-triazol-3-one収率 22.2%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 702Ethanol溶媒2 回HCID 962Water溶媒

反応条件

温度
110 °C

実験手順

A vial was charged with a slurry of 4-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (100 mg, 0.256 mmol), (2,4-dichlorophenyl)boronic acid (98 mg, 0.511 mmol), tetrakis(triphenylphosphine)palladium(0) (29.5 mg, 0.026 mmol) and tripotassium phosphate (217 mg, 1.022 mmol) in ethanol (4.0 mL) and water (4.00 mL) then purged with nitrogen and sealed with a standard teflon septa (crimped aluminum seal). The reaction was heated in an aluminum block at 110° C. for 2 h. The cooled reaction was diluted with ethanol then evaporated under reduced pressure to a yellow residue. The residue was triturated from methanol and the filtered methanol layer was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 20-70% acetonitrile w/0.1% TFA/water w/0.1% TFA). The desired product fractions were combined and evaporated in vacuo to a residue that was recrystallized from hexanes/ethyl acetate to afford the title compound as a white solid (26 mg, 21.8%). MS(ES)+ m/e 457.0, 459.2 [M+H]+, chlorine pattern.

後処理

  1. customthen purged with nitrogen
  2. customsealed with a standard teflon
  3. custom(crimped aluminum seal)
  4. customThe cooled reaction
  5. customthen evaporated under reduced pressure to a yellow residue
  6. customThe residue was triturated from methanol
  7. customthe filtered methanol layer was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 20-70% acetonitrile w/0.1% TFA/water w/0.1% TFA)
  8. customevaporated in vacuo to a residue that
  9. customwas recrystallized from hexanes/ethyl acetate

出典と根拠

ORDレコード
ord-9b3c67d208f945eaa73cd1f9d15b9445
出典データセット
uspto-grants-2016_05
特許番号
US09340529B2

反応ノート

読み込み中…