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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 2035991
ノート
印刷プレビュー

反応式

HRID 2035991 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 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 178418397
HCID 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-6f0f7a8410224848beb8e7ce9449a39e
出典データセット
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08575154B2

反応ノート

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