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

HRID 131496Notes

Reaction equation

HRID 131496 reaction equation
[CH3:1][C:2]1[S:11][C:10]2[NH:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[N:6]=[C:5]([N:16]3[CH2:21][CH2:20][NH:19][C@@H:18]([CH2:22][CH2:23][OH:24])[CH2:17]3)[C:4]=2[N:3]=1.C=O.[C:27](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:41]C(Cl)C>C(=O)(O)[O-].[Na+]>[ClH:41].[ClH:41].[CH3:27][N:19]1[CH2:20][CH2:21][N:16]([C:5]2[C:4]3[N:3]=[C:2]([CH3:1])[S:11][C:10]=3[NH:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[N:6]=2)[CH2:17][C@@H:18]1[CH2:22][CH2:23][OH:24]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 63651,1-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 135525257(S)-2-[4-(2-methyl-4H-3-thia-1,4,9-triazabenzo[f]azulene-10-yl)-piperazin-2-yl]-ethanol

Product 1

HCID 136384144(S)-2-[1-Methyl-4-(2-methyl-4H-3-thia-1,4,9-triazabenzo[f]azulene-10-yl)piperazin-2-yl]ethanol dihydrochlorideYield 46%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

Combine material from Example 300 (0.080 g, 0.233 mmol), formaldehyde (25 μL, 0.303 mmol, 37% aqueous solution), and sodium triacetoxyborohydride (74 mg, 0.349 mmol) in dichloroethane (8 mL) and stir at room temperature overnight. 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. Purify by flash chromatography, eluting with a step gradient starting with dichloromethane going to 6% 2N ammonia-methanol in dichloromethane, to obtain the free base of the title compound (0.038 g, 0.106 mmol, 46%). 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 as a brown solid: mass spectrum (APCI): m/z=358.3 (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. customPurify by flash chromatography
  5. washeluting with a step gradient

Sources & evidence

ORD record
ord-dc38df52f9c645e8b62e172714c152c2
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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