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

HRID 131466

Reaktionsgleichung

Reaktionsgleichung von HRID 131466
[C:1](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C=O.[CH3:17][O:18][CH2:19][CH2:20][C@@H:21]1[NH:26][CH2:25][CH2:24][N:23]([C:27]2[C:36]3[CH:35]=[C:34]([CH:37]([CH3:39])[CH3:38])[S:33][C:32]=3[NH:31][C:30]3[CH:40]=[CH:41][CH:42]=[CH:43][C:29]=3[N:28]=2)[CH2:22]1>ClC(Cl)C.C(=O)(O)[O-].[Na+]>[NH3:23].[CH3:17][O:18][CH2:19][CH2:20][C@@H:21]1[N:26]([CH3:1])[CH2:25][CH2:24][N:23]([C:27]2[C:36]3[CH:35]=[C:34]([CH:37]([CH3:39])[CH3:38])[S:33][C:32]=3[NH:31][C:30]3[CH:40]=[CH:41][CH:42]=[CH:43][C:29]=3[N:28]=2)[CH2:22]1

Komponenten

7

Edukt 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 136090342(S)-10-[3-(2-Methoxy-ethyl)-piperazin-1-yl]-2-isopropyl-4H-3-thia-4,9-diaza-benzo[f]azulene

Produkt 2

HCID 222AmmoniaHCID 136090373(S)-10-[3-(2-Methoxy-ethyl)-4-methyl-piperazin-1-yl]-2-isopropyl-4H-3-thia-4,9-diaza-benzo[f]azuleneAusbeute 149,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 63651,1-DichloroethaneLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

Add sodium triacetoxyborohydride (0.15 g, 0.71 mmol) and aqueous formaldehyde (37% w/w, 0.05 mL, 0.62 mmol) to a solution of (S)-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-isopropyl-4H-3-thia-4,9-diaza-benzo[f]azulene (0.18 g, 0.47 mmol) in dichloroethane (12 mL) and stir. After 5 hours, dilute with a saturated aqueous solution of sodium bicarbonate, and separate the layers. Extract the aqueous layer with dichloromethane (3×), combine organics, and dry (sodium sulfate), filter, and concentrate under reduced pressure to an oil (0.24 g). Purify the oil by flash chromatography, eluting with a gradient of a 5% solution of 2M ammonia in methanol, in dichloromethane (0-100% over 30 minutes), and then with a 5% solution of 2M ammonia in methanol, in dichloromethane to give the title compound (0.14 g, 74%): mass spectrum (APCI, m/e): 399 (M+1); NMR (1H, 300 MHz, DMSO-d6) δ 7.63 (s, 1H), 6.79 (m, 3H), 6.66 (m, 1H), 6.30 (s, 1H), 3.70 (m, 2H), 3.35-3.28 (m, 2H), 3.20 (s, 3H), 2.99-2.88 (m, 2H), 2.80-2.60 (m, 2H), 2.29-2.05 (m, 5H), 1.66 (m, 2H), 1.17 (d, 6H, J=7.5 Hz).

Aufarbeitung

  1. customseparate the layers
  2. extractionExtract the aqueous layer with dichloromethane (3×)
  3. dry with materialdry (sodium sulfate)
  4. filtrationfilter
  5. concentrationconcentrate under reduced pressure to an oil (0.24 g)
  6. customPurify the oil by flash chromatography
  7. washeluting with a gradient of a 5% solution of 2M ammonia in methanol, in dichloromethane (0-100% over 30 minutes)

Quellen und Nachweise

ORD-Eintrag
ord-24a9d3a1a3e94e91a9c686bf31857925
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07384934B2

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