Potassium Carbonate → tert-Butyl [(5-{[4-(2-tert-butylphenyl)piperazin-1-yl]carbonyl}pyridin-3-yl)oxy]acetate

HRID 534900

反応式

HRID 534900 の反応式
Cl.Cl.[C:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)([CH3:6])([CH3:5])[CH3:4].[OH:19][C:20]1[CH:21]=[C:22]([C:26]([OH:28])=O)[CH:23]=[N:24][CH:25]=1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.Br[CH2:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55].C(=O)([O-])[O-].[K+].[K+]>O.CN(C)C=O.C(N(CC)CC)C>[C:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[CH2:18][CH2:17][N:16]([C:26]([C:22]2[CH:21]=[C:20]([O:19][CH2:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH:25]=[N:24][CH:23]=2)=[O:28])[CH2:15][CH2:14]1)([CH3:6])([CH3:4])[CH3:5]

参加物

10

反応物 6

HCID 11430Potassium CarbonateHCID 340375-Hydroxynicotinic acidHCID 79177tert-Butyl bromoacetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 667511491-(2-Tert-butylphenyl)piperazine dihydrochloride

生成物 1

HCID 66751333tert-Butyl [(5-{[4-(2-tert-butylphenyl)piperazin-1-yl]carbonyl}pyridin-3-yl)oxy]acetate収率 68%

試薬・触媒・溶媒 3

HCID 962Water溶媒2 回HCID 6228Dimethylformamide溶媒2 回HCID 8471Triethylamine溶媒

実験手順

A mixture of 1-(2-tert-butylphenyl)piperazine dihydrochloride obtained in Reference Example 1 (500 mg), 5-hydroxypyridine-3-carboxylic acid (287 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (403 mg), 1-hydroxy-1H-benzotriazole monohydrate (322 mg), triethylamine (0.488 mL), and N,N-dimethylformamide (5 mL) was stirred at room temperature for 16 h. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to provide a powder (LC/MS (ESI+) m/z: 340 (M+H)+). A mixture of the powder, tert-butyl bromoacetate (683 mg), potassium carbonate (691 mg), and N,N-dimethylformamide (10 mL) was stirred at 60° C. for 5 h. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by flash column chromatography (silica gel, 90:10-50:50 hexane/ethyl acetate) to provide the title compound (530 mg, 68%) as crystals.

後処理

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customto provide a powder (LC/MS (ESI+) m/z: 340 (M+H)+)
  6. stirringwas stirred at 60° C. for 5 h
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe ethyl acetate layer was washed with saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solvent was evaporated under reduced pressure
  11. customthe residue was purified by flash column chromatography (silica gel, 90:10-50:50 hexane/ethyl acetate)

出典と根拠

ORDレコード
ord-1592e319a7094da195ccc565a1fcb5eb
出典データセット
uspto-grants-2014_10
特許番号
US08853215B2

関連ノート

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