Potassium Carbonate → 2-(3-(3-(4-(Tert-butoxycarbonyl)piperazin-1-yl)phenoxy)azetidin-1-yl)-5-chloronicotinic acid

HRID 72463

反応式

HRID 72463 の反応式
[OH:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:27][C:28]1[CH:29]=[N:30][C:31]([N:38]2[CH2:41][CH:40](OS(C)(=O)=O)[CH2:39]2)=[C:32]([CH:37]=1)[C:33]([O:35]C)=[O:34].[OH-].[Na+]>CN(C)C=O>[C:17]([O:16][C:14]([N:11]1[CH2:12][CH2:13][N:8]([C:4]2[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=2)[O:1][CH:40]2[CH2:41][N:38]([C:31]3[N:30]=[CH:29][C:28]([Cl:27])=[CH:37][C:32]=3[C:33]([OH:35])=[O:34])[CH2:39]2)[CH2:9][CH2:10]1)=[O:15])([CH3:20])([CH3:19])[CH3:18]

参加物

6

反応物 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 18669061tert-Butyl 4-(3-hydroxyphenyl)piperazine-1-carboxylateHCID 86697874Methyl 5-chloro-2-(3-((methylsulfonyl)oxy)azetidin-1-yl)nicotinate

生成物 1

HCID 679581532-(3-(3-(4-(Tert-butoxycarbonyl)piperazin-1-yl)phenoxy)azetidin-1-yl)-5-chloronicotinic acid

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
120 °C

実験手順

To a solution of tert-butyl 4-(3-hydroxyphenyl)piperazine-1-carboxylate (D18) (143.18 mg, 0.514 mmole) in dimethylformamide (2 ml), potassium carbonate (71 mg, 0.514 mmol) and the reaction mixture was heated 2 h at 80° C. methyl 5-chloro-2-(3-((methylsulfonyl)oxy)azetidin-1-yl)nicotinate (D63) (150 mg, 0.467 mmol) in dimethylformamide (2 ml) was added dropwise and the resulting mixture stirred 21 h at 120° C. After cooling at room temperature, 1M NaOH (0.935 ml) was added and the mixture stirred 1 h at 120° C. After cooling the reaction mixture was extracted with diethylether (2×10 ml) and the aqueous was evaporated in vacuo. The residue was purified by SPE-Si cartridge (5 g) eluting with a mixture dichloromethane/methanol from 100/0 to 80/20. Collected fractions, after solvent evaporation afforde the title compound (D110) (155 mg)

後処理

  1. additionwas added dropwise
  2. temperatureAfter cooling at room temperature
  3. stirringthe mixture stirred 1 h at 120° C
  4. temperatureAfter cooling the reaction mixture
  5. extractionwas extracted with diethylether (2×10 ml)
  6. customthe aqueous was evaporated in vacuo
  7. customThe residue was purified by SPE-Si cartridge (5 g)
  8. washeluting with a mixture dichloromethane/methanol from 100/0 to 80/20
  9. customCollected fractions, after solvent evaporation afforde the title compound (D110) (155 mg)

出典と根拠

ORDレコード
ord-cc660e40c4514ed698b84628d03b181e
出典データセット
uspto-grants-2014_09
特許番号
US08828987B2

関連ノート

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