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

HRID 131465Notes

Reaction equation

HRID 131465 reaction equation
[O:1]([CH2:8][CH2:9][C@@H:10]1[NH:15][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]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=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][O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 63651,1-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 135457500(S)-10-[3-(2-phenoxyethyl)piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene

Product 1

HCID 136384273(S)-10-[4-Methyl-3-(2-phenoxyethyl)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-phenoxyethyl)piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene, formaldehyde (1.1 equiv, 37% aqueous solution), and sodium triacetoxyborohydride (1.5 equiv.) 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 as the dihydrochloride salt 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 (0.059 g, 0.129 mmol, 8%) as an orange-solid. Mass spectrum (APCI): m/z=433.2 (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-d707ae1657bc4ae3b3242b621e9e69d5
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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