Citric Acid → N-[5-(4-Bromophenyl)-6-(2-hydroxyethoxy)-4-pyrimidinyl]-N′-propylsulfamide

HRID 1484489노트

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HRID 1484489 반응식
[CH3:1][CH2:2][CH2:3][NH:4][S:5]([NH:8][C:9]1[N:14]=[CH:13][N:12]=[C:11](Cl)[C:10]=1[C:16]1[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][CH:17]=1)(=[O:7])=[O:6].CC([O-])(C)C.[K+].C([O:33][CH2:34][CH2:35][OH:36])(C)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>Cl[Ti](Cl)(Cl)Cl.O.C1(C)C=CC=CC=1>[CH3:1][CH2:2][CH2:3][NH:4][S:5]([NH:8][C:9]1[N:14]=[CH:13][N:12]=[C:11]([O:33][CH2:34][CH2:35][OH:36])[C:10]=1[C:16]1[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][CH:17]=1)(=[O:7])=[O:6]

참가 물질

8

반응물 4

HCID 311Citric AcidHCID 242322-(Tert-butoxy)ethan-1-olHCID 23665647Potassium tert-butoxideHCID 71500858N-[5-(4-Bromophenyl)-6-chloro-4-pyrimidinyl]-N'-propylsulfamide

생성물 1

HCID 70813943N-[5-(4-Bromophenyl)-6-(2-hydroxyethoxy)-4-pyrimidinyl]-N′-propylsulfamide수율 86%

시약·촉매·용매 3

HCID 24193Titanium Tetrachloride촉매HCID 962Water용매2회HCID 1140Toluene용매2회

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온도
20 °C

실험 절차

N-(5-(4-bromophenyl)-6-chloropyrimidin-4-yl)propane-1-sulfamide (100 g; 0.246 mol; see Preparation A) and KOtBu (110 g; 0.99 mol; 4.0 eq.) were charged into a 2 L reactor. Toluene (1 L) was added. The resulting suspension was stirred at 20° C. for 5 min. 2-(tert-butoxy)ethanol (97 mL; 0.74 mol; 3.0 eq.) was added dropwise. After completion of the addition, the reaction mixture was heated to 85° C. for 2 h. After completion of the reaction, the mixture was cooled down to 20° C. Water (0.5 L) was added, followed by the addition of 10% aq. citric acid (0.5 L). The layers were separated. The org. phase was washed with brine 3 times (0.5 L each) and azeotropically dried with toluene (1 L) to a volume of approx. 1 L. The reaction mixture was heated to 50° C. A 1M solution of TiCl4 in toluene (420 mL, 0.42 mol; 1.7 eq.) was added dropwise with vigorous stirring. After completion of the addition, it was stirred at 35° C. for 20 h. Water (0.75 L) was added and the resulting beige suspension was stirred for 15 h. It was filtered off, rinsed with toluene (300 mL) and dried to afford the title compound as a white solid (91 g; 86% yield; purity (LC-MS): 100% a/a).

후처리

  1. additionwere charged into a 2 L reactor
  2. additionAfter completion of the addition
  3. temperaturethe reaction mixture was heated to 85° C. for 2 h
  4. customAfter completion of the reaction
  5. temperaturethe mixture was cooled down to 20° C
  6. customThe layers were separated
  7. washphase was washed with brine 3 times (0.5 L each)
  8. dry with materialazeotropically dried with toluene (1 L) to a volume of approx. 1 L
  9. temperatureThe reaction mixture was heated to 50° C
  10. additionAfter completion of the addition, it
  11. stirringwas stirred at 35° C. for 20 h
  12. stirringthe resulting beige suspension was stirred for 15 h
  13. filtrationIt was filtered off
  14. washrinsed with toluene (300 mL)
  15. customdried

출처 및 근거

ORD 기록
ord-ab70cb4c6c1b474cb1988f4e00c1983c
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09422249B2

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