Formaldehyde → (S)-10-[3-(2-methoxy-ethyl)-4-methyl-piperazin-1-yl]-2 isopropyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene

HRID 131498Notes

Reaction equation

HRID 131498 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][C@@H:5]1[NH:10][CH2:9][CH2:8][N:7]([C:11]2[C:20]3[N:19]=[C:18]([CH:21]([CH3:23])[CH3:22])[S:17][C:16]=3[NH:15][C:14]3[CH:24]=[CH:25][CH:26]=[CH:27][C:13]=3[N:12]=2)[CH2:6]1.C=O.[C:30](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(=O)(O)[O-].[Na+]>[CH3:1][O:2][CH2:3][CH2:4][C@@H:5]1[N:10]([CH3:30])[CH2:9][CH2:8][N:7]([C:11]2[C:20]3[N:19]=[C:18]([CH:21]([CH3:23])[CH3:22])[S:17][C:16]=3[NH:15][C:14]3[CH:24]=[CH:25][CH:26]=[CH:27][C:13]=3[N:12]=2)[CH2:6]1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 135485511(S)-10-[3-(2-Methoxyethyl)piperazin-1-yl]-2-isopropyl-4H-3-thia-1,4,9-triazabenzo[f]azulene

Product 1

HCID 135401180(S)-10-[3-(2-methoxy-ethyl)-4-methyl-piperazin-1-yl]-2 isopropyl-4H-3-thia-1,4,9-triaza-benzo[f]azuleneYield 90%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Combine (S)-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-isopropyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene (0.181 g, 0.469 mmol), formaldehyde (50 μL, 0.610 mmol, 37%), and sodium triacetoxyborohydride (0.149 g, 0.704 mmol) in dichloroethane (12 mL) and stir at room temperature for 2 hours. 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)-10-[3-(2-methoxy-ethyl)-4-methyl-piperazin-1-yl]-2 isopropyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene (0.168 g, 0.420 mmol, 90%) as a yellow oil: mass spectrum (APCI): m/z=400.3 (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 the title compound as a brown foam. Exact Mass, Calc: 400.2171; Found: 400.2171.

Workup

  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

Sources & evidence

ORD record
ord-d48cb4c507564aa19a8e054f5fd43ea0
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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