Formaldehyde → (S)-6-fluoro-10-[3-(3-methoxy-propyl)-4-methyl-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene

HRID 131472노트

반응식

HRID 131472 반응식
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:14]=[C:13]([N:15]3[CH2:20][CH2:19][NH:18][C@@H:17]([CH2:21][CH2:22][CH2:23][O:24][CH3:25])[CH2:16]3)[C:12]3[CH:11]=[C:10]([CH3:26])[S:9][C:8]=3[NH:7][C:6]=2[CH:27]=1.C=O.[C:30](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(=O)(O)[O-].[Na+]>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:14]=[C:13]([N:15]3[CH2:20][CH2:19][N:18]([CH3:30])[C@@H:17]([CH2:21][CH2:22][CH2:23][O:24][CH3:25])[CH2:16]3)[C:12]3[CH:11]=[C:10]([CH3:26])[S:9][C:8]=3[NH:7][C:6]=2[CH:27]=1

참가 물질

6

반응물 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 58626005(s)-6-fluoro-10-[3-(3-methoxy-propyl)-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene

생성물 1

HCID 58625979(S)-6-fluoro-10-[3-(3-methoxy-propyl)-4-methyl-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene수율 89%

시약·촉매·용매 2

HCID 63651,1-Dichloroethane용매HCID 516892Sodium Bicarbonate용매

실험 절차

Combine (S)-6-fluoro-10-[3-(3-methoxy-propyl)-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene (0.105 g, 0.270 mmol), formaldehyde (31 μL, 0.378 mmol, 37%), and sodium triacetoxyborohydride (0.086 g, 0.405 mmol) in dichloroethane (6 mL) and stir at room temperature overnight. Dilute the mixture with saturated sodium bicarbonate and extract three times with methylene chloride. Combine the organic layers, dry over sodium sulfate and concentrate under reduced pressure to give the crude product. Purification by flash chromatography, eluting with a step gradient starting with dichloromethane going to 5% 2N ammonia-methanol in dichloromethane gives (S)-6-fluoro-10-[3-(3-methoxy-propyl)-4-methyl-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene (0.097 g, 0.240 mmol, 89%) as a yellow oil. Mass spectrum (APCI): m/z=403.1 (M+1). Isolate clean product as the corresponding dihydrochloride in the following manner: dissolve the yellow foam in ethanol (5 mL) and add a solution of about 5 equivalents of HCl in ethanol (5 mL). Evaporate the mixture to obtain (S)-6-fluoro-10-[3-(3-methoxy-propyl)-4-methyl-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene dihydrochloride.

후처리

  1. extractionextract three times with methylene chloride
  2. dry with materialdry over sodium sulfate
  3. concentrationconcentrate under reduced pressure
  4. customto give the crude product
  5. customPurification by flash chromatography
  6. washeluting with a step gradient

출처 및 근거

ORD 기록
ord-83606cff7eb14bf6a83948dca573ebdf
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07384934B2

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