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Sodium Carbonate → 1-(5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-4-fluoro-2-vinylphenyl)-4-methyl-1H-tetrazol-5(4H)-one

HRID 633397
ノート
印刷プレビュー

反応式

HRID 633397 の反応式
[CH3:1][C:2]1([CH3:35])[CH2:10][C@H:9]([NH:11][C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[C:21]([F:34])=[CH:22][C:23](Br)=[C:24]([N:26]4[C:30](=[O:31])[N:29]([CH3:32])[N:28]=[N:27]4)[CH:25]=3)[N:13]=2)[CH2:8][C@H:7]2[N:3]1[CH2:4][CH2:5][CH2:6]2.C(=O)([O-])[O-].[Na+].[Na+].[CH:42](B1OC(C)(C)C(C)(C)O1)=[CH2:43]>C(COC)OC.C(O)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][C:2]1([CH3:35])[CH2:10][C@H:9]([NH:11][C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[C:21]([F:34])=[CH:22][C:23]([CH:42]=[CH2:43])=[C:24]([N:26]4[C:30](=[O:31])[N:29]([CH3:32])[N:28]=[N:27]4)[CH:25]=3)[N:13]=2)[CH2:8][C@H:7]2[N:3]1[CH2:4][CH2:5][CH2:6]2
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 3

HCID 10340Sodium CarbonateHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 867044941-(5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-2-bromo-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)-one

生成物 1

HCID 867044961-(5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-4-fluoro-2-vinylphenyl)-4-methyl-1H-tetrazol-5(4H)-one収率 93.6%

試薬・触媒・溶媒 4

HCID 178418476HCID 178418476、化合物触媒HCID 702Ethanol溶媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
110 °C

実験手順

1-(5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-2-bromo-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)-one (301.9 mg, 0.55 mmol) was weighed out and added to a reaction tube with magnetic stir bar. It was dissolved in 24 mL of a solution of dimethoxyethane, ethanol, and water in a ratio of 7:3:2, respectively. Sodium carbonate (174.6 mg, 1.65 mmol) was weighed out, and vinylboronic acid pinacol ester (0.205 mL, 1.21 mmol) was then added. The solution was subjected to vigorous sub-surface nitrogen sparging. Bis(triphenylphosphine)palladium(II) dichloride (17.3 mg, 0.025 mmol) was weighed out and added, the tube was sealed under nitrogen, and the reaction was heated overnight at 110° C. The reaction solution was then combined with a 0.162 mmol pilot reaction run under the same conditions. This was concentrated directly onto silica, and purified by column chromatography. Pure fractions were combined, concentrated, and dried under high vacuum to give 256.0 mg of the title compound (72% total).

後処理

  1. additionadded to a reaction tube with magnetic stir bar
  2. additionadded
  3. customthe tube was sealed under nitrogen
  4. customThe reaction solution was then combined with a 0.162 mmol pilot reaction
  5. concentrationThis was concentrated directly onto silica
  6. custompurified by column chromatography
  7. concentrationconcentrated
  8. customdried under high vacuum

出典と根拠

ORDレコード
ord-a31ee93e1e8b4071bff57ac1149d807e
出典データセット
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09321763B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート