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

HRID 2035995ノート

反応式

HRID 2035995 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][C:3]=1[F:11].FC(F)(F)S(O[C:18]1[CH:23]=[CH:22][C:21]([C@H:24]2[C:29]3=[N:30][S:31](=[O:35])(=[O:34])[CH2:32][CH2:33][N:28]3[CH2:27][CH2:26][CH2:25]2)=[CH:20][CH:19]=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][C:5]([C:18]2[CH:19]=[CH:20][C:21]([C@H:24]3[C:29]4=[N:30][S:31](=[O:35])(=[O:34])[CH2:32][CH2:33][N:28]4[CH2:27][CH2:26][CH2:25]3)=[CH:22][CH:23]=2)=[CH:4][C:3]=1[F:11]

参加物

8

反応物 3

HCID 10340Sodium CarbonateHCID 27786564-Chloro-3-fluorophenylboronic 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 66748508(9S)-9-(4'-chloro-3'-fluorobiphenyl-4-yl)-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide収率 5.2%

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 (4-chloro-3-fluorophenyl)boronic acid (85.0 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 16 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) and concentrated. The residue was dissolved in MeCN/DMSO (1900/100 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 to give the title compound (5.00 mg) as a white solid.

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. concentrationconcentrated
  5. dissolutionThe residue was dissolved in MeCN/DMSO (1900/100 μM)
  6. custompurified by preparative HPLC (C18, eluted with water in acetonitrile containing 0.1% TFA)
  7. extractionextracted with EtOAc
  8. washwashed with brine
  9. customThe organic layer was separated
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-bcfcd274b0dc4b139d147149fb004c1f
出典データセット
uspto-grants-2013_11
特許番号
US08575154B2

反応ノート

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