Sodium Carbonate → (9S)-9-(2'-chlorobiphenyl-4-yl)-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide

HRID 1622838ノート

反応式

HRID 1622838 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1B(O)O.FC(F)(F)S(O[C:17]1[CH:22]=[CH:21][C:20]([C@H:23]2[C:28]3=[N:29][S:30](=[O:34])(=[O:33])[CH2:31][CH2:32][N:27]3[CH2:26][CH2:25][CH2:24]2)=[CH:19][CH:18]=1)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>CCO.O.CN(C=O)C.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>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:17]1[CH:18]=[CH:19][C:20]([C@H:23]2[C:28]3=[N:29][S:30](=[O:34])(=[O:33])[CH2:31][CH2:32][N:27]3[CH2:26][CH2:25][CH2:24]2)=[CH:21][CH:22]=1

参加物

8

反応物 3

HCID 10340Sodium CarbonateHCID 27343222-Chlorophenylboronic acidHCID 866636154-[(9S)-2,2-dioxido-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazin-9-yl]phenyl trifluoromethanesulfonate

生成物 1

HCID 66748636(9S)-9-(2'-chlorobiphenyl-4-yl)-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide収率 42.2%

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 702Ethanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

Tetrakis(triphenylphosphine)palladium(0) (16.0 mg) was added to a mixture of (2-chlorophenyl)boronic acid (76.0 mg), 4-[(9S)-2,2-dioxido-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazin-9-yl]phenyl trifluoromethanesulfonate (100 mg) and sodium carbonate (51.4 mg) in EtOH (3 ml), water (1.5 mL) and DMF (dry) (2 ml). The mixture was stirred at 50° C. under nitrogen for 19 hr. Silica-gel was added and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc), dissolved in MeCN/DMSO (4700/300 μM) and purified by preparative HPLC (C18, eluted with water in acetonitrile containing 0.1% TFA). The desired fractions were neutralized with sat. NaHCO3 aq., extracted with EtOAc and washed with brine. The organic layer was separated, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was crystallized from MeCN-THF/hexane to give the title compound (38.4 mg) as colorless crystals.

後処理

  1. additionSilica-gel was added
  2. customthe volatiles were removed in vacuo
  3. customwas purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc)
  4. dissolutiondissolved in MeCN/DMSO (4700/300 μM)
  5. custompurified by preparative HPLC (C18, eluted with water in acetonitrile containing 0.1% TFA)
  6. extractionextracted with EtOAc
  7. washwashed with brine
  8. customThe organic layer was separated
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was crystallized from MeCN-THF/hexane

出典と根拠

ORDレコード
ord-808fbee5fbf544d892ff3d36caa5118e
出典データセット
uspto-grants-2014_07
特許番号
US08778934B2

反応ノート

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