Formaldehyde → (R)-10-(4-Methyl-3-phenoxymethyl-piperazin-1-yl)-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene

HRID 131463Notes

Reaction equation

HRID 131463 reaction equation
C=O.[O:3]([CH2:10][C@@H:11]1[NH:16][CH2:15][CH2:14][N:13]([C:17]2[C:26]3[CH:25]=[C:24]([CH3:27])[S:23][C:22]=3[NH:21][C:20]3[CH:28]=[CH:29][CH:30]=[CH:31][C:19]=3[N:18]=2)[CH2:12]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[CH:33](Cl)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH3:33][N:16]1[CH2:15][CH2:14][N:13]([C:17]2[C:26]3[CH:25]=[C:24]([CH3:27])[S:23][C:22]=3[NH:21][C:20]3[CH:28]=[CH:29][CH:30]=[CH:31][C:19]=3[N:18]=2)[CH2:12][C@@H:11]1[CH2:10][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 4

HCID 712FormaldehydeHCID 63651,1-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 135546110(R)-10-(3-Phenoxymethyl-piperazin-1-yl)-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene

Product 1

HCID 136090327(R)-10-(4-Methyl-3-phenoxymethyl-piperazin-1-yl)-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azuleneYield 63.3%

Procedure

Add aqueous 37% formaldehyde (1.1 eqiv) to a solution of (R)-10-(3-phenoxymethyl-piperazin-1-yl)-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene (520 mg) in dichloroethane (60 mL per 1 mmol non-alkylated starting material). Stir the mixture 2 minutes and add sodium triacetoxyborohydride (1.5 mmol per 1 mmol non-alkylated starting material). Stir the suspension for 30 minutes and quench with a saturated aqueous solution of sodium bicarbonate. Extract the aqueous phase 3 times with dichloromethane and combine the organic phases, dry over magnesium sulfate, filter and concentrate. Purify the residue via chromatography on silica gel (methylene chloride/methanol (90:10) to provide the title compound as a yellow solid (265 mg, 49%): mp 74-88° C.; 1H NMR (CDCl3) δ 2.28 (s, 3H), 2.47 (s, 3H), 2.50-2.39 (m, 1H), 2.66-2.58 (m, 1H), 2.91 (dt, 1H), 3.11 (dd, 1H), 3.26 (dt, 1H), 3.93 (bd, 1H), 4.14-4.03 (m, 3H), 4.91 (bs, 1H), 6.31-6.29 (m, 1H), 6.59 (dt, 1H), 7.00-6.86 (m, 5H), 7.03 (dd, 1H), 7.32-7.27 (m, 2H); MS (APCI) m/z (rel intensity) 419.3 (100).

Workup

  1. stirringStir the suspension for 30 minutes
  2. customquench with a saturated aqueous solution of sodium bicarbonate
  3. extractionExtract the aqueous phase 3 times with dichloromethane
  4. dry with materialdry over magnesium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the residue via chromatography on silica gel (methylene chloride/methanol (90:10)

Sources & evidence

ORD record
ord-0ccb58c03a7249eb8ec8d5af67a58770
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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