Acetic Acid → 3,4-Dihydro-2-[(5-methyl-1H-imidazol-4-yl)methyl]-[1]benzothieno[3,2-c]pyridin-1(2H)-one maleate

HRID 703786

反応式

HRID 703786 の反応式
[C:1]1(=[O:14])[C:6]2[C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[S:9][C:5]=2[CH2:4][CH2:3][NH:2]1.[H-].[Na+].Cl[CH2:18][C:19]1[N:20]=[CH:21][N:22](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[C:23]=1[CH3:24].[C:44]([OH:47])(=[O:46])[CH3:45].CN(C=[O:52])C>C1COCC1.O>[C:1]([OH:14])(=[O:52])/[CH:6]=[CH:45]\[C:44]([OH:47])=[O:46].[CH3:24][C:23]1[NH:22][CH:21]=[N:20][C:19]=1[CH2:18][N:2]1[CH2:3][CH2:4][C:5]2[S:9][C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[C:6]=2[C:1]1=[O:14]

参加物

8

反応物 5

HCID 176Acetic AcidHCID 6228Dimethylformamide2 回HCID 24758Sodium hydrideHCID 110469654-(Chloromethyl)-5-methyl-1-trityl-1H-imidazoleHCID 200749053,4-Dihydro-[1]benzothieno[3,2-c]pyridin-1(2H)-one

生成物 1

HCID 700932433,4-Dihydro-2-[(5-methyl-1H-imidazol-4-yl)methyl]-[1]benzothieno[3,2-c]pyridin-1(2H)-one maleate

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of 3,4-dihydro-[1]benzothieno[3,2-c]pyridin-1(2H)- one (152mg) in dry DMF (3ml) was added dropwise to a stirred, ice-cooled suspension of sodium hydride (78% dispersion in oil; 29mg) in dry DMF (1ml) under nitrogen and stirring was continued at room temperature for 1.5h. A suspension of 4-chloromethyl-5-methyl-1-(triphenylmethyl)-1H-imidazole (560mg) in dry THF (4ml) was added dropwise and stirring was continued at room temperature for 18h. A mixture of acetic acid (5ml), water (5ml) and THF (5ml) was added and the solution was heated at 100° for 1h, cooled, evaporated and treated with 8% aqueous sodium bicarbonate (35ml). The aqueous phase was extracted with ethyl acetate (2×25ml) and the combined, dried organic extracts were evaporated to give an oil. This was purified by SPCC eluting with System A (923:70:7) to give the free base of the title compound as a foam (32 mg). This was further purified by FCC eluting with System A (89:10:1) to give an oil (20mg). This was dissolved in hot ethanol (3ml) and treated with a solution of maleic acid (8mg) in ethanol (1ml). The resultant solution was evaporated to give the title compound (25mg), m.p. 143°-145°, t.l.c. (System A, 89:10:1) Rf 0.27.

後処理

  1. temperaturecooled
  2. additionwas added dropwise
  3. stirringstirring
  4. waitwas continued at room temperature for 18h
  5. additionwas added
  6. temperaturecooled
  7. customevaporated
  8. additiontreated with 8% aqueous sodium bicarbonate (35ml)
  9. extractionThe aqueous phase was extracted with ethyl acetate (2×25ml)
  10. customdried organic extracts were evaporated
  11. customto give an oil
  12. customThis was purified by SPCC
  13. washeluting with System A (923:70:7)

出典と根拠

ORDレコード
ord-c85195182443411ea56ef5160f6242fd
出典データセット
uspto-grants-1991_01
特許番号
US04985422

関連ノート

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