Hydrochloric Acid → HCID 58529343, compound

HRID 1973030Notes

Reaction equation

HRID 1973030 reaction equation
C(OC([N:11]1[CH2:16][CH2:15][CH2:14][C@@H:13]([C:17]2[N:25]3[C:20]([C:21]([NH2:26])=[N:22][CH:23]=[N:24]3)=[C:19]([C:27]3[CH:28]=[CH:29][C:30]4[C:34]([CH:35]=3)=[N:33][N:32]([CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:31]=4)[CH:18]=2)[CH2:12]1)=O)C1C=CC=CC=1.Cl>>[CH2:36]([N:32]1[CH:31]=[C:30]2[C:34]([CH:35]=[C:27]([C:19]3[CH:18]=[C:17]([C@@H:13]4[CH2:14][CH2:15][CH2:16][NH:11][CH2:12]4)[N:25]4[C:20]=3[C:21]([NH2:26])=[N:22][CH:23]=[N:24]4)[CH:28]=[CH:29]2)=[N:33]1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 58529570HCID 58529570, compound

Product 1

HCID 58529343HCID 58529343, compoundYield 23.7%

Procedure

The product from step 1 (256 mg) was mixed with 6N aqueous HCl and heated to reflux for 30 min (HPLC analysis shows complete consumption of SM) and then allowed to cool to rt. The mixture was concentrated in vacuo and then dissolved in water (1 mL) and acetonitrile was added drop wise with stirring (˜10 mL). The mixture was stirred and a precipitate began to form. The mixture was stirred for 1 hour and the precipitate was collected by filtration, washed with acetonitrile and dried in a vacuum oven overnight and this fraction (presumably HCl salt) was set aside. The filtrate was concentrated in vacuo and the process repeated (0.5 mL of water and 20 mL of acetonitrile). The mixture was stirred overnight and then cooled in an ice bath for 1 hour and the precipitate was collected by filtration and dried in a vacuum oven (set aside). The filtrate from this process was poured through a column containing an acidic ion exchange resin. The column was washed with acetonitrile and the product eluted by washing the column with 2M NH3 in MeOH. The filtrate was concentrated to give 46 mg of the title compound as a free base. 1H NMR (300 MHz, DMSO-d6) δ 8.75 (s, 1H), 7.89 (s, 1H), 7.79 (d, 1H), 7.68 (s, 1H), 7.39-7.23 (m, 5H), 7.14 (d, 1H), 6.58 (s, 1H), 5.63 (s, 2H), 3.30-3.12 (m, 2H), 2.92 (d, 1H), 2.58-2.30 (m, 3H), 2.06 (m, 1H), 1.69-1.43 (m, 2H). ES-MS m/z 424.2 [M+H]+, HPLC RT (min) 2.17. Spectral properties of the HCl salt: 1H NMR (300 MHz, DMSO-d6) 9.22 (m, 1H), 9.06 (m, 1H), 8.59 (s, 1H), 8.07 (s, 1H), 7.83 (d, 1H), 7.62 (s, 1H), 7.38-7.25 (m, 5H), 7.13 (d, 1H), 6.78 (s, 1H), 5.62 (s, 2H), 3.64 (m, 1H), 3.52 (d, 1H), 3.31 (d, 1H), 3.09 (dd, 1H), 2.90 (dd, 1H), 2.10 (d, 1H), 1.96-1.69 (m, 3H). ES-MS m/z 424.4 [M+H]+, HPLC RT (min) 2.01.

Workup

  1. temperatureheated
  2. temperatureto reflux for 30 min
  3. custom(HPLC analysis shows complete consumption of SM)
  4. concentrationThe mixture was concentrated in vacuo
  5. dissolutiondissolved in water (1 mL)
  6. additionacetonitrile was added drop wise
  7. stirringThe mixture was stirred
  8. customto form
  9. stirringThe mixture was stirred for 1 hour
  10. filtrationthe precipitate was collected by filtration
  11. washwashed with acetonitrile
  12. customdried in a vacuum oven overnight
  13. concentrationThe filtrate was concentrated in vacuo
  14. stirringThe mixture was stirred overnight
  15. temperaturecooled in an ice bath for 1 hour
  16. filtrationthe precipitate was collected by filtration
  17. customdried in a vacuum oven (
  18. additionThe filtrate from this process was poured through a column
  19. additioncontaining an acidic ion exchange resin
  20. washThe column was washed with acetonitrile
  21. washthe product eluted
  22. washby washing the column with 2M NH3 in MeOH
  23. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-1cbc66f2fca0444b8071ec6679d01e91
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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