Acetaldehyde → (S)-10-[4-Ethyl-3-(2-methoxyethyl)piperazin-1-yl]-2-isopropyl-4H-3-thia-1,4,9-triazabenzo[f]azulene dihydrochloride

HRID 131501Notes

Reaction equation

HRID 131501 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.[CH:28](=O)[CH3:29].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:45]C(Cl)C>C(=O)(O)[O-].[Na+]>[ClH:45].[ClH:45].[CH2:28]([N:10]1[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][C@@H:5]1[CH2:4][CH2:3][O:2][CH3:1])[CH3:29]

Participants

6

Reactant 4

HCID 177AcetaldehydeHCID 63651,1-DichloroethaneHCID 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 136384261(S)-10-[4-Ethyl-3-(2-methoxyethyl)piperazin-1-yl]-2-isopropyl-4H-3-thia-1,4,9-triazabenzo[f]azulene dihydrochlorideYield 71%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

Combine (S)-10-[3-(2-methoxyethyl)piperazin-1-yl]-2-isopropyl 4H-3-thia-1,4,9-triazabenzo[f]azulene (0.103 g, 0.267 mmol), acetaldehyde (30 μL, 0.534 mmol), and sodium triacetoxyborohydride (0.085 g, 0.401 mmol) in dichloroethane (7 mL) and stir, at room temperature for 6 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 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 the free base of the title compound (0.79 g, 71%) as a yellow foam: mass spectrum (APCI): m/z=414.2 (M+1). Isolate clean product as the corresponding dihydrochloride in the manner described in Example 319. Exact Mass, Calc: 414.2328; Found: 414.2326.

Workup

  1. extractionextract three times with dichloromethane
  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-1065ab0a9ab341d59bf52ba1effc0311
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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