Sodium hydride → 6-[4-(2-Amino-ethyl)-phenoxy]-nicotinamide

HRID 228336

反応式

HRID 228336 の反応式
C(OC(=O)[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)(C)(C)C.[H-].[Na+].Cl[C:21]1[CH:29]=[CH:28][C:24]([C:25]([NH2:27])=[O:26])=[CH:23][N:22]=1>CN(C=O)C>[NH2:7][CH2:8][CH2:9][C:10]1[CH:11]=[CH:12][C:13]([O:16][C:21]2[CH:29]=[CH:28][C:24]([C:25]([NH2:27])=[O:26])=[CH:23][N:22]=2)=[CH:14][CH:15]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 804566-ChloronicotinamideHCID 11831452tert-butyl N-(2-(4-hydroxyphenyl)ethyl)carbamate

生成物 1

HCID 597300176-[4-(2-Amino-ethyl)-phenoxy]-nicotinamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Treat [2-(4-hydroxyphenyl)ethyl]carbamic acid tert-butyl ester (534.3 mg, 2.2 mmol) with NaH (80% in mineral oil, 78.0 mg (2.6 mmol) in anhydrous DMF (10 mL) at room temperature for 30 minutes. Add 6-chloronicotinamide (343.8 mg, 2.2 mmol) and heat the mixture at 80° C. overnight. Quench the reaction with H2O and concentrate to dryness, using xylenes to remove DMF as an azeotrope. Suspend the residue in MeOH and filter with thorough MeOH and CH2Cl2 rinse. Concentrate the filtrate and purify by flash chromatography, eluting with 75:15:10 EtOAc/CH2Cl2/2.0 M NH3 in MeOH. Deprotect the BOC group with 1:1 TFA/CH2Cl2 (16 mL) at room temperature overnight. Concentrate and purify by an SCX column, washing with MeOH and then eluting with 2.0 M NH3 in MeOH: MS ES+ 297.9 (M+H+K)+, HRMS calcd for C14H16N3O2 258.1243 (M+H)+, found 258.1235 time 0.40 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 5-95% over 19 min], tR=6.93 min. 100% purity.

後処理

  1. customQuench
  2. customthe reaction with H2O
  3. concentrationconcentrate to dryness
  4. customto remove DMF as an azeotrope
  5. filtrationfilter with thorough MeOH and CH2Cl2
  6. washrinse
  7. concentrationConcentrate the filtrate
  8. custompurify by flash chromatography
  9. washeluting with 75:15:10 EtOAc/CH2Cl2/2.0 M NH3 in MeOH
  10. customat room temperature
  11. customovernight
  12. concentrationConcentrate
  13. custompurify by an SCX column
  14. washwashing with MeOH
  15. washeluting with 2.0 M NH3 in MeOH
  16. custom258.1235 time 0.40 min
  17. customHPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 5-95% over 19 min], tR=6.93 min

出典と根拠

ORDレコード
ord-ab595828b76f409d976939d6dff86dcf
出典データセット
uspto-grants-2009_07
特許番号
US07560463B2

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