Formaldehyde → (S)-2-[4(2-isopropyl-4H-3-thia-1,4,9-triazabenzo[f]azulen-10-yl)-1-methylpiperazin-2-yl]ethanol

HRID 131497Notes

Reaction equation

HRID 131497 reaction equation
[CH:1]([C:4]1[S:13][C:12]2[NH:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[N:8]=[C:7]([N:18]3[CH2:23][CH2:22][NH:21][CH:20]([CH2:24][CH2:25][OH:26])[CH2:19]3)[C:6]=2[N:5]=1)([CH3:3])[CH3:2].C=O.[C:29](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(=O)(O)[O-].[Na+]>[CH:1]([C:4]1[S:13][C:12]2[NH:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[N:8]=[C:7]([N:18]3[CH2:23][CH2:22][N:21]([CH3:29])[C@@H:20]([CH2:24][CH2:25][OH:26])[CH2:19]3)[C:6]=2[N:5]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 1363885862-[4-(2-Isopropyl-4H-3-thia-1,4,9-triaza-benzo[f]azulen-10-yl)-piperazin-2-yl]-ethanol

Product 1

HCID 135430628(S)-2-[4(2-isopropyl-4H-3-thia-1,4,9-triazabenzo[f]azulen-10-yl)-1-methylpiperazin-2-yl]ethanolYield 35.3%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Combine 2-[4-(2-Isopropyl-4H-3-thia-1,4,9-triaza-benzo[f]azulen-10-yl)-piperazin-2-yl]-ethanol (0.161 g, 0.433 mmol), formaldehyde (46 μL, 0.563 mmol, 37%), and sodium triacetoxyborohydride (0.138 g, 0.650 mmol) in dichloroethane (15 mL) and stir at room temperature overnight. 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 8% 2N ammonia-methanol in dichloromethane gives (S)-2-[4(2-isopropyl-4H-3-thia-1,4,9-triazabenzo[f]azulen-10-yl)-1-methylpiperazin-2-yl]ethanol (0.059 g, 0.153 mmol, 35%) as a yellow oil. Mass spectrum (APCI): m/z=386.4 (M+1). Isolate clean product as the corresponding dihydrochloride in the following manner: dissolve the yellow oil in ethanol (5 mL) and add a solution of about 5 equivalents of HCl in ethanol (5 mL). Evaporate the mixture to obtain (S)-2-[4-(2-isopropyl-4H-3-thia-1,4,9-triazabenzo[f]azulen-10-yl)-1-methylpiperazin-2-yl]ethanol dihydrochloride.

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-6b9fba69dd1742628b50ff50bb07b9a7
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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