Formaldehyde → (s)-2-Methyl-10-[4-methyl-3-(2-thiophen-3-yl-ethyl)-piperazin-1-yl]-4h-3-thia-4,9-diaza-benzo[f]azulene dihydrochloride

HRID 1350440Notes

Reaction equation

HRID 1350440 reaction equation
C=O.[CH3:3][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][C@@H:20]([CH2:24][CH2:25][C:26]4[CH:30]=[CH:29][S:28][CH:27]=4)[CH2:19]3)[C:6]=2[CH:5]=1.[C:31](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)[Cl:46]>C(=O)(O)[O-].[Na+]>[ClH:46].[ClH:46].[CH3:3][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]([CH3:31])[C@@H:20]([CH2:24][CH2:25][C:26]4[CH:30]=[CH:29][S:28][CH:27]=4)[CH2:19]3)[C:6]=2[CH:5]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 6344DichloromethaneHCID 5049666Sodium triacetoxyborohydrideHCID 135932169HCID 135932169, compound

Product 1

HCID 136464469(s)-2-Methyl-10-[4-methyl-3-(2-thiophen-3-yl-ethyl)-piperazin-1-yl]-4h-3-thia-4,9-diaza-benzo[f]azulene dihydrochlorideYield 59%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

Add formaldehyde (45 μL, 0.56 mmol, 37% in water) to a solution of (S)-2-methyl-10-[3-(2-thiophen-3-yl-ethyl)-piperazin-1-yl]-4H-3-thia-4,9-diaza-benzo[f]azulene (210 mg, 0.51 mmol) in methylene chloride (6 mL). Stir 15 min at ambient temperature. Add sodium triacetoxyborohydride (163 mg, 0.77 mmol) and stir 2h at ambient temperature. Dilute with saturated sodium bicarbonate solution and extract with methylene chloride. Dry the extracts with sodium sulfate, filter and concentrate the filtrate. Purify by radial silica gel chromatography using a 2 mm plate and 2N ammonia in methanol-methylene chloride (2%) as the eluent to give 127 mg (59%) of the free base of the title compound. Crystallize the dihydrochloride salt from ethyl acetate and ethanol to give the title compound: mass spectrum (ion spray): m/z=423 (M+1), 421 (M−1). Analysis calculated for C23H28Cl2N4S2.0.2HCl.0.3H2O: C, 54.35; H, 5.71; N, 11.01; Cl, 15.35. Found: C, 54.10; H, 5.34; N, 10.99; Cl, 15.00. HR-MS calculated for C23H27N4S2423.1677. Found 423.1656.

Workup

  1. extractionextract with methylene chloride
  2. dry with materialDry the extracts with sodium sulfate
  3. filtrationfilter
  4. concentrationconcentrate the filtrate
  5. customPurify by radial silica gel chromatography

Sources & evidence

ORD record
ord-303da1b1af594f3c96076aaf2ba31b40
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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