Nitric Acid → N~4~-[4-(2,4-Dimethyl-1,3-Thiazol-5-Yl)pyrimidin-2-Yl]-N~1~,N~1~-Dimethyl-2-Nitrobenzene-1,4-Diamine

HRID 132531

반응식

HRID 132531 반응식
[N+:1]([O-:4])(O)=[O:2].[CH3:5][C:6]1[S:7][C:8]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([N:25]([CH3:27])[CH3:26])=[CH:21][CH:20]=3)[N:13]=2)=[C:9]([CH3:11])[N:10]=1.[N+]([O-])(OC(=O)C)=O.C([O-])(O)=O.[Na+]>CC(OC(C)=O)=O>[CH3:5][C:6]1[S:7][C:8]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([N:25]([CH3:27])[CH3:26])=[C:21]([N+:1]([O-:4])=[O:2])[CH:20]=3)[N:13]=2)=[C:9]([CH3:11])[N:10]=1

참가 물질

6

반응물 4

HCID 944Nitric AcidHCID 11557Acetyl nitrateHCID 447962N-(4-(2,4-Dimethyl-thiazol-5-YL)-pyrimidin-2-YL)-N',N'-dimethyl-benzene-1,4-diamineHCID 516892Sodium Bicarbonate

생성물 1

HCID 6539302N~4~-[4-(2,4-Dimethyl-1,3-Thiazol-5-Yl)pyrimidin-2-Yl]-N~1~,N~1~-Dimethyl-2-Nitrobenzene-1,4-Diamine수율 57.6%

시약·촉매·용매 1

HCID 7918Acetic Anhydride용매2회

실험 절차

HNO3 (69% aq, 24 μL, 0.36 mmol) was added dropwise to Ac2O (1 mL) at room temperature, keeping the internal temperature below 25° C. The mixture was stirred at room temperature for 15 min before cooling to −5° C. in an ice-MeOH bath. Compound N-[4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl]-N′,N′-dimethyl-benzene-1,4-diamine (50 mg, 0.15 mmol) was slurried in Ac2O (1 mL) and added dropwise to the cooled solution of acetyl nitrate. The mixture was stirred with cooling for 1 h then a further 2 h at room temperature. The mixture was poured into ice-water (20 mL) and the pH was adjusted to 7-8 by addition of saturated aq NaHCO3 solution. The mixture was extracted with EtOAc. The combined organics were washed with brine, dried on MgSO4, and filtered. The solvent was evaporated in vacuo to give a dark solid, which was purified by flash chromatography, eluted with heptane/EtOAc to afford 32 mg of the title compound as a pale reddish solid. RP-HPLC: tR=12.7 min (10-70% MeCN in 0.1% aq CF3COOH over 20 min, 1 mL/min, purity>95%). 1H-NMR (DMSO-d6): δ 2.62 (s, 3H, CH3), 2.64 (s, 3H, CH3), 2.74 (s, 6H, CH3), 7.09 (d, 1H, J=5.1 Hz, pyrimidinyl-H), 7.23 (d, 1H, J=8.8 Hz, Ph-H), 7.77 (dd, 1H, J=8.7, 2.7 Hz, Ph-H), 8.39 (d, 1H, J=2.7 Hz), 8.51 (d, 1H, J=5.1 Hz, pyrimidinyl-H), 9.81 (br. s, 1H, NH).

후처리

  1. customthe internal temperature below 25° C
  2. temperaturebefore cooling to −5° C. in an ice-MeOH bath
  3. stirringThe mixture was stirred
  4. temperaturewith cooling for 1 h
  5. customa further 2 h
  6. customat room temperature
  7. extractionThe mixture was extracted with EtOAc
  8. washThe combined organics were washed with brine
  9. customdried on MgSO4
  10. filtrationfiltered
  11. customThe solvent was evaporated in vacuo
  12. customto give a dark solid, which
  13. customwas purified by flash chromatography
  14. washeluted with heptane/EtOAc

출처 및 근거

ORD 기록
ord-a7d00bdc3cdb44f9a6a9174ec4ad3e69
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07388015B2

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