Formaldehyde → (S)-10-[3-(2-Methoxyethyl)-4-methylpiperazin-1-yl]-2-cyclopentyl 4H-3-thia-1,4,9-triazabenzo[f]azulene dihydrochloride

HRID 131499Notes

Reaction equation

HRID 131499 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]4[CH2:25][CH2:24][CH2:23][CH2:22]4)[S:17][C:16]=3[NH:15][C:14]3[CH:26]=[CH:27][CH:28]=[CH:29][C:13]=3[N:12]=2)[CH2:6]1.C=O.[C:32](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:46]C(Cl)C>C(=O)(O)[O-].[Na+]>[ClH:46].[ClH:46].[CH3:1][O:2][CH2:3][CH2:4][C@@H:5]1[N:10]([CH3:32])[CH2:9][CH2:8][N:7]([C:11]2[C:20]3[N:19]=[C:18]([CH:21]4[CH2:25][CH2:24][CH2:23][CH2:22]4)[S:17][C:16]=3[NH:15][C:14]3[CH:26]=[CH:27][CH:28]=[CH:29][C:13]=3[N:12]=2)[CH2:6]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 63651,1-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 135517425(S)-10-[3-(2-methoxyethyl)-piperazin-1-yl]-2-cyclopentyl-4H-3-thia-1,4,9-triazabenzo[f]azulene

Product 1

HCID 136388587(S)-10-[3-(2-Methoxyethyl)-4-methylpiperazin-1-yl]-2-cyclopentyl 4H-3-thia-1,4,9-triazabenzo[f]azulene dihydrochlorideYield 91%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

Combine (S)-10-[3-(2-methoxyethyl)-piperazin-1-yl]-2-cyclopentyl-4H-3-thia-1,4,9-triazabenzo[f]azulene (0.364 g, 0.884 mmol), formaldehyde (93 μL, 1.15 mmol, 37%), and sodium triacetoxyborohydride (0.281 g, 1.33 mmol) in dichloroethane (15 mL) and stir at room temperature for 4 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 a solid residue. 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 (0.342 g; 0.804 mmol, 91%) as a yellow oil: mass spectrum (APCI): m/z=386.4 (M+1). Isolate the 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 hydrochloric acid in ethanol (5 mL); then remove the solvent under vacuum: Exact Mass, Calc: 426.2328; Found: 426.2329.

Workup

  1. extractionextract three times with dichloromethane
  2. dry with materialdry over sodium sulfate
  3. concentrationconcentrate under reduced pressure
  4. customto give a solid residue
  5. customPurify by flash chromatography
  6. washeluting with a step gradient

Sources & evidence

ORD record
ord-7239dcf81df54b638437587037b54dda
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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