Propanal → (S)-10-[3-(2-Methoxy-ethyl)-4-propyl-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene

HRID 131503Notes

Reaction equation

HRID 131503 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH:15](=O)[CH2:16][CH3:17].[CH3:19][O:20][CH2:21][CH2:22][C@@H:23]1[NH:28][CH2:27][CH2:26][N:25]([C:29]2[C:38]3[N:37]=[C:36]([C:39]([F:42])([F:41])[F:40])[S:35][C:34]=3[NH:33][C:32]3[CH:43]=[CH:44][CH:45]=[CH:46][C:31]=3[N:30]=2)[CH2:24]1>ClC(Cl)C>[CH3:19][O:20][CH2:21][CH2:22][C@@H:23]1[N:28]([CH2:15][CH2:16][CH3:17])[CH2:27][CH2:26][N:25]([C:29]2[C:38]3[N:37]=[C:36]([C:39]([F:41])([F:42])[F:40])[S:35][C:34]=3[NH:33][C:32]3[CH:43]=[CH:44][CH:45]=[CH:46][C:31]=3[N:30]=2)[CH2:24]1

Participants

5

Reactant 3

HCID 527PropanalHCID 5049666Sodium triacetoxyborohydrideHCID 135457486(S)-10-[3-(2-Methoxy-ethyl)-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene

Product 1

HCID 136090397(S)-10-[3-(2-Methoxy-ethyl)-4-propyl-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azuleneYield 74%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

Add sodium triacetoxyborohydride (0.273 g, 1.29 mmol), and then propionaldehyde (0.083 mL, 1.15 mmol) to (S)-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene (0.353 g, 0.858 mmol) in anhydrous dichloroethane (15 mL) and stir at ambient temperature overnight. Add saturated aqueous sodium bicarbonate and extract aqueous phase with dichloromethane. Wash organics with saturated aqueous sodium chloride, and dry (sodium sulfate), filter, and concentrate under reduced pressure to a residue (0.29 g). Purify the residue by flash chromatography, eluting with a gradient of a 3% solution of 2M ammonia in methanol, in dichloromethane, (0-100%) to give the title compound (0.287 g, 74%): mass spectrum (APCI, m/e): 454 (M+1); NMR (1H, 300 MHz, DMSO-d6): δ 8.46 (s, 1H), 6.96-6.82 (m, 3H), 6.71 (m, 1H), 3.46 (br. m, 3H), 3.31-3.17 (m, 3H), 3.15 (s, 3H), 2.73 (m, 1H), 2.58-2.44 (m, 2H), 2.31 (m, 2H), 1.67 (m, 2H), 1.40 (m, 2H), 0.83 (t, 3H, J=7.5 Hz).

Workup

  1. extractionAdd saturated aqueous sodium bicarbonate and extract aqueous phase with dichloromethane
  2. dry with materialWash organics with saturated aqueous sodium chloride, and dry (sodium sulfate)
  3. filtrationfilter
  4. concentrationconcentrate under reduced pressure to a residue (0.29 g)
  5. customPurify the residue by flash chromatography
  6. washeluting with a gradient of a 3% solution of 2M ammonia in methanol, in dichloromethane, (0-100%)

Sources & evidence

ORD record
ord-9e84d0cc3eb64360aa62c459bd2fda8e
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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