Formaldehyde → Ammonia

HRID 1350466Notes

Reaction equation

HRID 1350466 reaction equation
[C:1](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C=O.[CH2:17]([C:21]1[S:30][C:29]2[NH:28][C:27]3[CH:31]=[CH:32][CH:33]=[CH:34][C:26]=3[N:25]=[C:24]([N:35]3[CH2:40][CH2:39][NH:38][C@@H:37]([CH2:41][CH2:42][C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)[CH2:36]3)[C:23]=2[N:22]=1)[CH2:18][CH2:19][CH3:20]>ClC(Cl)C.C(=O)(O)[O-].[Na+]>[NH3:22].[CH2:17]([C:21]1[S:30][C:29]2[NH:28][C:27]3[CH:31]=[CH:32][CH:33]=[CH:34][C:26]=3[N:25]=[C:24]([N:35]3[CH2:40][CH2:39][N:38]([CH3:1])[C@@H:37]([CH2:41][CH2:42][C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)[CH2:36]3)[C:23]=2[N:22]=1)[CH2:18][CH2:19][CH3:20]

Participants

7

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 136005542(S)-2-Butyl-10-(3-phenethyl-piperazin-1-yl)-4H-3-thia-1,4,9-triaza-benzo[f]azulene

Product 2

HCID 222AmmoniaHCID 136005597(S)-2-Butyl-10-(4-methyl-3-phenethyl-piperazin-1-yl)-4H-3-thia-1,4,9-triaza-benzo[f]azulene

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Add sodium triacetoxyborohydride and aqueous formaldehyde (37%w/w, to a solution of (S)-2-Butyl-10-(3-phenethyl-piperazin-1-yl)-4H-3-thia-1,4,9-triaza-benzo[f]azulene (0.50 g, 1.1 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 (0.19 g): Mass spectrum (APCI+, m/e): 460 (M+1); 1H NMR (300 MHz, CDCl3), δ (ppm): 7.39–7.11 (m, 5H), 7.11–6.95 (m, 2H), 6.94–6.81 (m, 1H), 6.69–6.57 (m, 1H), 5.01 (s, 1H), 4.40–3.93 (br. m, 1H), 3.34–3.16 (m, 1H), 3.08–2.92 (m, 1H), 2.93–2.40 (m, 7H), 2.40–2.23 (m, 4H), 2.06–1.51 (m, 4H), 1.38 (d, 2H, J=7.1 Hz), 0.90 (t, 3H, J=7.1 Hz).

Workup

  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)

Sources & evidence

ORD record
ord-8e958ac7fbb744fb940b25c4a2d6093e
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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