Toluene → (S)-(1-(3-(4-methylphenyl)-7-(3,4-difluorophenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-2-yl)methanol

HRID 872090ノート

反応式

HRID 872090 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]3[N:15]=[C:16]([CH3:19])[C:17](I)=[C:13]3[N:12]=[C:11]([N:20]3[CH2:24][CH2:23][CH2:22][C@H:21]3[CH2:25][OH:26])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].[CH3:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.C1(C)C=CC=CC=1.C([O-])(O)=O.[Na+]>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.C(O)C>[CH3:27][C:28]1[CH:33]=[CH:32][C:31]([C:17]2[C:16]([CH3:19])=[N:15][N:14]3[C:9]([C:4]4[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[CH:3]=4)=[CH:10][C:11]([N:20]4[CH2:24][CH2:23][CH2:22][C@H:21]4[CH2:25][OH:26])=[N:12][C:13]=23)=[CH:30][CH:29]=1

参加物

7

反応物 4

HCID 1140TolueneHCID 79799Tolylboronic acidHCID 516892Sodium BicarbonateHCID 68026319(S)-(1-(7-(3,4-difluorophenyl)-3-iodo-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-2-yl)methanol

生成物 1

HCID 66635694(S)-(1-(3-(4-methylphenyl)-7-(3,4-difluorophenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-2-yl)methanol収率 60%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 702Ethanol溶媒

反応条件

温度
85 °C

実験手順

(S)-(1-(7-(3,4-Difluorophenyl)-3-iodo-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-2-yl)methanol (74 mg), 4-methylphenylboronic acid (27 mg) and tetrakis(triphenylphosphine)palladium (10 mg) are added to toluene (7 mL), ethanol (3 mL) and 1 N NaHCO3 aqueous solution (1.5 mL) and stirred overnight under argon atmosphere at 85° C. After cooling to room temperature, the reaction solvent is removed by distillation under reduced pressure. The remainder is extracted with ethyl acetate and water. The organic layer is washed with brine and dehydrated with anhydrous MgSO4. The dehydrated organic layer is distilled under reduced pressure, concentrated and purified by column chromatography to yield the target compound (41 mg).

後処理

  1. temperatureAfter cooling to room temperature
  2. customthe reaction solvent is removed by distillation under reduced pressure
  3. extractionThe remainder is extracted with ethyl acetate and water
  4. washThe organic layer is washed with brine
  5. distillationThe dehydrated organic layer is distilled under reduced pressure
  6. concentrationconcentrated
  7. custompurified by column chromatography

出典と根拠

ORDレコード
ord-7aa4a47a0d774ee5b93ed1580c441299
出典データセット
uspto-grants-2015_03
特許番号
US08975264B2

反応ノート

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