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

HRID 1350357Notes

Reaction equation

HRID 1350357 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:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH2:19]3)[C:6]=2[CH:5]=1.[C:32](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[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]([CH3:32])[C@@H:20]([CH2:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH2:19]3)[C:6]=2[CH:5]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 1360056242-methyl-10-(3-(S)-phenethyl-piperazin-1-yl)-4H-3-thia-4,9-diazabenzo[f]azulene

Product 1

HCID 135797743(S)-2-methyl-10-(4-methyl-3-phenethyl-piperazin-1-yl)-4H-3-thia-4,9-diaza-benzo[f]azuleneYield 68.7%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

Add aqueous 37% formaldehyde (45 mL, 0.55 mmol) to a solution of 2-methyl-10-(3-(S)-phenethyl-piperazin-1-yl)-4H-3-thia-4,9-diazabenzo[f]azulene (200 mg, 0.5 mmol) in dichloroethane (30 mL). Stir the mixture 2 minutes and add sodium triacetoxyborohydride (159 mg, 0.75 mmol). 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 (MgSO4), filter and concentrate. Purify the residue via chromatography eluting with methylene chloride/methanol (90:10) to provide the title compound as a yellow solid (143 mg, 67%): mp 87–91° C.: 1H NMR (CDCl3): δ1.78 (m, 1H), 1.96 (m, 1H), 2.22 (m, 1H), 2.32 (s, 3H), 2.35 (s, 3H), 2.38 (ddd, 1H), 2.58 (ddd, 1H), 2.75 (ddd, 1H), 2.86 (ddd, 1H), 2.94 (dd, 1H), 3.16 (ddd, 1H), 3.90 (m, 1H), 4.05 (m, 1H), 4.94 (s, 1H), 6.30 (s, 1H), 6.60 (d, 1H), 6.87 (t, 1H), 6.98 (t, 1H), 7.04 (d, 1H), 7.17–7.32 (m, 5H); MS (APCI) m/z (rel intensity) 417 (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 (MgSO4)
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the residue via chromatography
  8. washeluting with methylene chloride/methanol (90:10)

Sources & evidence

ORD record
ord-8b819a4455e546de8bc0cadcf759dd4e
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

Loading…