Acetic Acid → (S)-5-(3-aminopropyl)-1-(5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)-1,3-dihydroimidazole-2-thione hydrochloride

HRID 1245776ノート

反応式

HRID 1245776 の反応式
[ClH:1].[F:2][C:3]1[CH:12]=[C:11]([F:13])[CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][C@H:7]([NH2:14])[CH2:8]2.[Si](O[CH2:23][C:24](=O)[CH2:25][CH2:26][CH2:27][N:28]1C(=O)C2C(=CC=CC=2)C1=O)(C(C)(C)C)(C)C.[S-:40][C:41]#[N:42].[K+].C(O)(=O)C.[BH4-].[Na+]>C(OCC)(=O)C.O>[ClH:1].[NH2:28][CH2:27][CH2:26][CH2:25][C:24]1[N:14]([C@H:7]2[CH2:6][CH2:5][C:4]3[C:9](=[CH:10][C:11]([F:13])=[CH:12][C:3]=3[F:2])[CH2:8]2)[C:41](=[S:40])[NH:42][CH:23]=1

参加物

8

反応物 5

HCID 176Acetic Acid2 回HCID 516872Potassium thiocyanateHCID 4311764Sodium borohydrideHCID 116029612-[5-(tert-Butyldimethylsilanyloxy)4-oxopentyl]isoindole-1,3-dioneHCID 66789737(S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride

生成物 1

HCID 11674895(S)-5-(3-aminopropyl)-1-(5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)-1,3-dihydroimidazole-2-thione hydrochloride

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

A stirred mixture of (S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl amine hydrochloride (0.22 g, 1.0 mmol), 2-[5-(tert-butyldimethylsilanyloxy)-4-oxopentyl]isoindole-1,3-dione (0.38 g, 1.05 mmol), potassium thiocyanate (0.11 g, 1.10 mmol), water (0.18 g, 1.0 mmol) and acetic acid (0.3 mL, 5.0 mmol) in ethyl acetate (3 mL) was refluxed for 7 hours, cooled to room temperature, washed by sodium bicarbonate solution, dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue was purified by column chromatography on silica using ethyl acetate-petroleum ether mixture as eluent. The resulting oil (0.18 g) was dissolved in a mixture of isopropanol (5 mL) and THF (2 mL). Water (0.8 mL) and sodium borohydride (0.066 g, 1.74 mmol) were added at room temperature and the mixture was stirred for 1.5 hours. Acetic acid (0.6 ml, 10 mmol) was added and the solution was refluxed for two hours then evaporated in vacuo to dryness. The residue was taken up into acetone, the solid was filtered off, and the filtrate was acidified with 2N HCl solution in ethyl acetate. The precipitate was collected and washed with acetone to afford crystals, which decomposed without melting.

後処理

  1. temperaturewas refluxed for 7 hours
  2. washwashed by sodium bicarbonate solution
  3. dry with materialdried over anhydrous magnesium sulphate
  4. customevaporated in vacuo
  5. customThe residue was purified by column chromatography on silica
  6. dissolutionThe resulting oil (0.18 g) was dissolved in a mixture of isopropanol (5 mL) and THF (2 mL)
  7. temperaturethe solution was refluxed for two hours
  8. customthen evaporated in vacuo to dryness
  9. filtrationthe solid was filtered off
  10. customThe precipitate was collected
  11. washwashed with acetone
  12. customto afford crystals, which

出典と根拠

ORDレコード
ord-4e5dbdc04c224b359d21aada6ef9d82f
出典データセット
uspto-grants-2006_10
特許番号
US07125904B2

反応ノート

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