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

HRID 1350388Notes

Reaction equation

HRID 1350388 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][C:24]4[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=4)[CH2:17]3)[C:4]=2[CH:3]=1.C=O.[CH2:32](Cl)[Cl:33].C(O[BH-](OC(=O)C)OC(=O)C)(=[O:37])C.[Na+]>C(=O)(O)[O-].[Na+]>[OH2:37].[ClH:33].[ClH:33].[ClH:33].[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][N:19]([CH3:32])[C@@H:18]([CH2:22][CH2:23][C:24]4[CH:25]=[CH:26][N:27]=[CH:28][CH:29]=4)[CH2:17]3)[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 6344DichloromethaneHCID 5049666Sodium triacetoxyborohydrideHCID 135932150HCID 135932150, compound

Product 1

HCID 1371945252-Methyl-10-(4-methyl-(s)-3-(2-pyridin-4-yl-ethyl)-piperazin-1-yl)-4h-3-thia-4,9-diaza-benzo[f]azulene trihydrochloride hydrate

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

Combine 2-methyl-10-((S)-3-(2-pyridin-4-yl-ethyl)-piperazin-1-yl)-4H-3-thia-4,9-diaza-benzo[f]azulene (380 mg, 0.94 mmol) and formaldehyde (82 μL, 1.04 mmol, 37% in water), and methylene chloride (10 mL). Stir 5 minutes at ambient temperature. Add sodium triacetoxyborohydride (300 mg, 1.41 mmol) and stir 30 minutes 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 silica gel chromatography using 2N ammonia in methanol-methylene chloride (1%–3%) as the eluent to give 345 mg of a brown foam. Purify again by silica gel chromatography using 2N ammonia in methanol-methylene chloride (0%–6.5%) as the eluent to give the free base. Crystallize as the trihydrochloride salt from ethyl acetate and ethanol to give the title compound (244 mg, 62%): mp 214–217° C. dec.; mass spectrum (ion spray): m/z=418 (M+1), 416 (M−1). Analysis calculated for C24H27N5S.3HCl·0.9H2O: C, 53.07; H, 5.90; N, 12.89. Found: C, 53.31; H, 5.54; N, 12.75.

Workup

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

Sources & evidence

ORD record
ord-9009eb1a89d9406eaed43428389b738d
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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