Formaldehyde → (S)-10-[4-Methyl-3-(2-phenylsulfanylethyl)piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene dihydrochloride

HRID 131482Notes

Reaction equation

HRID 131482 reaction equation
[C:1]1([S:7][CH2:8][CH2:9][C@@H:10]2[NH:15][CH2:14][CH2:13][N:12]([C:16]3[C:25]4[CH:24]=[C:23]([CH3:26])[S:22][C:21]=4[NH:20][C:19]4[CH:27]=[CH:28][CH:29]=[CH:30][C:18]=4[N:17]=3)[CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C=O.[C:33](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:47]C(Cl)C>C(=O)(O)[O-].[Na+]>[ClH:47].[ClH:47].[CH3:33][N:15]1[CH2:14][CH2:13][N:12]([C:16]2[C:25]3[CH:24]=[C:23]([CH3:26])[S:22][C:21]=3[NH:20][C:19]3[CH:27]=[CH:28][CH:29]=[CH:30][C:18]=3[N:17]=2)[CH2:11][C@@H:10]1[CH2:9][CH2:8][S:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 63651,1-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 136090413(S)-10-[3-(2-phenylsulfanyl-ethyl)piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene

Product 1

HCID 136384363(S)-10-[4-Methyl-3-(2-phenylsulfanylethyl)piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene dihydrochloride

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

Combine (S)-10-[3-(2-phenylsulfanyl-ethyl)piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene (0.118 g, 0.271 mmol), formaldehyde (24 μL, 0.299 mmol, 37% aqueous solution), and sodium triacetoxyborohydride (86 mg, 0.407 mmol) in dichloroethane (10 mL) and stir at room temperature for 2 hours. Dilute the mixture with saturated aqueous sodium bicarbonate and extract three times with dichloromethane. Combine the organic layers, dry over sodium sulfate and concentrate under reduced pressure. Purification by flash chromatography, eluting with a step gradient starting with dichloromethane going to 6% 2N ammonia-methanol in dichloromethane gives the free base of the title compound. Isolate clean product as the corresponding dihydrochloride by dissolving the free base in ethanol and adding a solution of 5 equivalents of hydrochloric acid in ethanol. Evaporating the solution and drying the salt provides the title compound (0.089 g, 0.189 mmol, 70%) as a brown solid. Mass spectrum (APCI): m/z=449.1 (M+1 of free base).

Workup

  1. extractionextract three times with dichloromethane
  2. dry with materialdry over sodium sulfate
  3. concentrationconcentrate under reduced pressure
  4. customPurification by flash chromatography
  5. washeluting with a step gradient

Sources & evidence

ORD record
ord-d207b8f88e0b488ab57cab6770e23b3a
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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