Potassium Iodide → 5-{3-[4-(5-Cyanoindol-3-yl)-1,2,5,6-tetrahydropyrid-1-yl]propoxy}-2-methylbenzothiazole

HRID 1016506

反応式

HRID 1016506 の反応式
[CH3:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH2:13][CH2:14]Cl)=[CH:7][C:5]=2[N:6]=1.[C:16]([C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[NH:23][CH:22]=[C:21]2[C:27]1[CH2:28][CH2:29][NH:30][CH2:31][CH:32]=1)#[N:17].[I-].[K+]>C(#N)C.O.[OH-].[NH4+].C(OCC)(=O)C>[C:16]([C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[NH:23][CH:22]=[C:21]2[C:27]1[CH2:28][CH2:29][N:30]([CH2:14][CH2:13][CH2:12][O:11][C:8]2[CH:9]=[CH:10][C:4]3[S:3][C:2]([CH3:1])=[N:6][C:5]=3[CH:7]=2)[CH2:31][CH:32]=1)#[N:17]

参加物

8

反応物 3

HCID 4875Potassium IodideHCID 113335543-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-carbonitrileHCID 184070592-Methyl-5-(3-chloropropoxyl)-benzothiazole

生成物 1

HCID 102028485-{3-[4-(5-Cyanoindol-3-yl)-1,2,5,6-tetrahydropyrid-1-yl]propoxy}-2-methylbenzothiazole収率 37.6%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒HCID 14923Ammonium Hydroxide溶媒

実験手順

A mixture of 2-methyl-5-(3-chloropropoxyl)-benzothiazole (3 g, 12.4 mmol), 5-cyano-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (3 g, 13.4 mmol) and a catalytic amount of potassium iodide in 50 ml of acetonitrile was stirred at 80° C. overnight. The reaction mixture was cooled, diluted with water, ammonium hydroxide and ethyl acetate. The two phases were separated and the aqueous phase was extracted with ethyl acetate twice. The organic phases were combined, washed with brined, dried over sodium sulfate and then concentrated under reduced pressure to a solid. This residual solid was subjected to a silica gel chromatography, eluting with 7% methanol in dichloromethane. Fractions shown to contain product were combined and concentrated to provide 2 g of the title compound in 35% yield as free base. The resulting free base was dissolved in methanol/dichloromethane and precipitated with excess HCl in ether. Recrystalization from ethanol give 1.8 g of the title compound as a light yellow solid. mp. 263-65° C. MS(CI) m+1=429. EA (C25H24N4 OS.1.7HCl): Theory: C, 61.21%; H, 5.28%; N, 11.42%. Found: C, 61.10%; H, 5.43%; N, 11.39%.

後処理

  1. temperatureThe reaction mixture was cooled
  2. customThe two phases were separated
  3. extractionthe aqueous phase was extracted with ethyl acetate twice
  4. washwashed with brined,
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure to a solid
  7. washeluting with 7% methanol in dichloromethane
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-1a07a0b309bc413491f7967027a90f80
出典データセット
uspto-grants-2002_11
特許番号
US06476051B2

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