Potassium Carbonate → 4-{4-[4-(Morpholine-4-sulfonyl)-phenyl]-pyrimidin-2-ylamino}benzoic Acid

HRID 2117311노트

반응식

HRID 2117311 반응식
[N:1]1([S:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16](=O)[CH3:17])=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl.[NH:20]([C:24]1[CH:33]=[CH:32][C:27]([C:28]([O:30]C)=[O:29])=[CH:26][CH:25]=1)[C:21]([NH2:23])=[NH:22].[C:34]([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>COC(OC)N(C)C>[N:1]1([S:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:17]=[CH:34][N:23]=[C:21]([NH:20][C:24]4[CH:33]=[CH:32][C:27]([C:28]([OH:30])=[O:29])=[CH:26][CH:25]=4)[N:22]=3)=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

참가 물질

6

반응물 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 7467651-[4-(4-Morpholinylsulfonyl)phenyl]ethanoneHCID 178498154HCID 178498154, 화합물

생성물 1

HCID 219059994-{4-[4-(Morpholine-4-sulfonyl)-phenyl]-pyrimidin-2-ylamino}benzoic Acid

시약·촉매·용매 1

HCID 78373Dimethylformamide dimethyl acetal용매

실험 절차

Crude 1-[4-(morpholine-4-sulfonyl)phenyl]ethanone (4.78 g, 18 mmol) was suspended in dimethyformamide dimethylacetal (50 mL) and refluxed for 12 h. The reaction was allowed to cool and the mixture was concentrated to about half of the original volume. The solution was then titurated with hexanes to precipitate the eneamino ketone intermediate. The eneamino ketone was filtered and washed with hexanes (2×50 mL), dried under vacuum, and then taken up in nPrOH (150 mL). To this solution was added added 4-guanidinobenzoic acid, methyl ester, hydrochloride salt (1.1 equiv, 3.7 g) and K2CO3 (3 equiv, 6.4 g). The mixture was stirred at reflux for 24 h. After this time, 10% NaOH (aq, 50 mL) was added, and the mixture was stirred at reflux for another 1 h. The mixture was then cooled to RT and concentrated to about half of the original volume. The pH of the mixture was then adjusted to pH 4-5 to precipitate the acid. 4-{4-[4-(morpholine-4-sulfonyl)phenyl]pyrimidin-2-ylamino}benzoic acid was immediately filtered and washed with water (50 mL), cold EtOH (50 mL), and then dried (4.6 g, 10.5 mmol, 68%): HPLC Retention Time; 6.6 min. (Method B) M+1, 441.0.

후처리

  1. temperaturerefluxed for 12 h
  2. temperatureto cool
  3. concentrationthe mixture was concentrated to about half of the original volume
  4. customto precipitate the eneamino ketone intermediate
  5. filtrationThe eneamino ketone was filtered
  6. washwashed with hexanes (2×50 mL)
  7. customdried under vacuum
  8. additionTo this solution was added
  9. temperatureat reflux for 24 h
  10. stirringthe mixture was stirred
  11. temperatureat reflux for another 1 h
  12. concentrationconcentrated to about half of the original volume
  13. customto precipitate the acid
  14. filtration4-{4-[4-(morpholine-4-sulfonyl)phenyl]pyrimidin-2-ylamino}benzoic acid was immediately filtered
  15. washwashed with water (50 mL), cold EtOH (50 mL)
  16. customdried (4.6 g, 10.5 mmol, 68%)

출처 및 근거

ORD 기록
ord-8d215828b01345daa878d06944be7fee
출처 데이터셋
uspto-grants-2008_10
특허 번호
US07442699B2

반응 노트

불러오는 중…