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

HRID 1246775

反応式

HRID 1246775 の反応式
[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+]>[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

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 7467651-[4-(4-Morpholinylsulfonyl)phenyl]ethanoneHCID 178498154HCID 178498154、化合物

生成物 1

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

試薬・触媒・溶媒 1

HCID 14798Sodium Hydroxide溶媒

実験手順

Crude 1-[4-(morpholine-4-sulfonyl)phenyl]ethanone (4.78 g, 18 mmol) was suspended in dimethylormamide 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.

後処理

  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%)

出典と根拠

ORDレコード
ord-3e451fb9cb51493798408a249da2ae44
出典データセット
uspto-grants-2006_10
特許番号
US07129242B2

関連ノート

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