Ammonia → HCID 16035375, compound

HRID 2234189Notes

Reaction equation

HRID 2234189 reaction equation
C(Cl)(=O)C(Cl)=O.[CH2:7]([N:9]([CH2:29][CH3:30])[CH2:10][CH2:11][N:12]([CH2:26][CH2:27]O)[C:13](=[O:25])[CH2:14][CH2:15][O:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH3:8].Cl.[NH2:32][CH2:33][CH2:34][C:35]1[C:43]2[S:42][C:41](=[O:44])[NH:40][C:39]=2[C:38]([OH:45])=[CH:37][CH:36]=1.C([BH3-])#N.[Na+].N>ClCCl.CO.O.C(O)(=O)C.C(N(CC)CC)C.CS(C)=O>[CH2:7]([N:9]([CH2:29][CH3:30])[CH2:10][CH2:11][N:12]([CH2:26][CH2:27][NH:32][CH2:33][CH2:34][C:35]1[C:43]2[S:42][C:41](=[O:44])[NH:40][C:39]=2[C:38]([OH:45])=[CH:37][CH:36]=1)[C:13](=[O:25])[CH2:14][CH2:15][O:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH3:8]

Participants

12

Reactant 5

HCID 222AmmoniaHCID 65578Oxalyl chlorideHCID 5003444Sodium cyanoborohydrideHCID 602075534-Hydroxy-7-(2-aminoethyl)-1,3-benzothiazol-2(3H)-one hydrochlorideHCID 68699870HCID 68699870, compound

Product 1

HCID 16035375HCID 16035375, compound

Reagents, catalysts & solvents 6

HCID 176Acetic AcidSolventHCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent4×HCID 8471TriethylamineSolvent

Procedure

A solution of dimethyl sulfoxide (0.10 g) in dichloromethane (1 mL) was added to oxalyl chloride (0.083 g) in dichloromethane (10 mL) at −78° C. The reaction was stirred for 15 minutes and then a solution of N-(2-diethylaminoethyl)-N-(2-hydroxyethyl)-3-phenethyloxy-propanamide (Example 12a), 0.20 g) in dichloromethane (1 mL+1 mL wash) was added and the reaction mixture was stirred for a further 15 minutes. Triethylamine (0.30 g) was added and the reaction mixture was allowed to warm to room temperature over 1 hour. The mixture was subsequently diluted (dichloromethane, 30 mL), the organics washed with saturated sodium hydrogencarbonate solution (20 mL) and then brine (20 mL), dried over anhydrous magnesium sulphate, filtered and concentrated in vacuo to give a crude aldehyde product which was used immediately. The crude product was dissolved in methanol (10 mL) and 7-(2-aminoethyl)-4-hydroxy-3H-benzothiazol-2-one hydrochloride (0.15 g) added along with acetic acid (0.1 mL) and water (0.1 mL). After stirring at room temperature for 30 minutes, sodium cyanoborohydride (0.022 g) was added and the reaction mixture was stirred overnight. Ammonia (7N in methanol, 1 mL) was added and the mixture was concentrated. The crude residue was purified by flash silica column chromatography eluting with 1% ammonia; 5%-7% methanol in dichloromethane. The isolated product was dissolved in dichloromethane and treated with 4 N hydrogen chloride in 1,4-dioxane (0.5 mL) and concentrated. The oily residue was triturated with ether, decanting the ether and concentrating to afford the titled compound as a white solid (0.032 g).

Workup

  1. stirringthe reaction mixture was stirred for a further 15 minutes
  2. washthe organics washed with saturated sodium hydrogencarbonate solution (20 mL)
  3. dry with materialbrine (20 mL), dried over anhydrous magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a crude aldehyde product which
  7. stirringAfter stirring at room temperature for 30 minutes
  8. stirringthe reaction mixture was stirred overnight
  9. concentrationthe mixture was concentrated
  10. customThe crude residue was purified by flash silica column chromatography
  11. washeluting with 1% ammonia
  12. dissolutionThe isolated product was dissolved in dichloromethane
  13. additiontreated with 4 N hydrogen chloride in 1,4-dioxane (0.5 mL)
  14. concentrationconcentrated
  15. customThe oily residue was triturated with ether
  16. customdecanting the ether
  17. concentrationconcentrating

Sources & evidence

ORD record
ord-86dffce4f56145d1b13fea2bfbf25ec6
Source dataset
uspto-grants-2010_05
Patent number
US07709511B2

Reaction notes

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