Ammonia → HCID 67165506, compound

HRID 553318Notes

Reaction equation

HRID 553318 reaction equation
C(OC(=O)[N:7]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1OCOC)[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH:16]=O)[CH:10]=1)(C)(C)C.[ClH:30].[NH2:31][CH2:32][CH:33]([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)[OH:34].C([BH3-])#N.[Na+].N.C[OH:52]>C(O)(=O)C>[ClH:30].[ClH:30].[OH:45][C:38]1[C:39]2[NH:40][C:41](=[O:44])[S:42][C:43]=2[C:35]([CH:33]([OH:34])[CH2:32][NH:31][CH2:16][CH2:15][C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([CH2:8][NH:7][CH2:18][C:19]3[CH:20]=[CH:21][CH:22]=[C:23]([OH:52])[CH:24]=3)[CH:10]=2)=[CH:36][CH:37]=1

Participants

7

Reactant 5

HCID 222AmmoniaHCID 887Methanol2×HCID 5003444Sodium cyanoborohydrideHCID 67164110HCID 67164110, compoundHCID 86628377HCID 86628377, compound

Product 1

HCID 67165506HCID 67165506, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of (2-methoxymethoxy-benzyl)-[3-(2-oxo-ethyl)-benzyl]-carbamic acid tert-butyl ester (116 mg) in methanol (1 mL) was added to a solution of 7-(2-amino-1-hydroxy-ethyl)-4-hydroxy-3H-benzothiazol-2-one hydrochloride (76 mg) in methanol (5 mL), the reaction mixture was treated with acetic acid (20 mg) followed by sodium cyanoborohydride (27 mg) and the resultant mixture was stirred for 5 hours. At the end of this time concentrated aqueous ammonia (0.5 mL) was added, the solvents were then removed under reduced pressure and the residue partitioned between ethyl acetate and saturated aqueous brine. The aqueous layer was re-extracted with ethyl acetate and the combined organic layers were dried, filtered and the solvent removed under reduced pressure. The residue was dissolved in trifluoroacetic acid (5 mL) and the solution allowed to stand at room temperature for 15 minutes, the solvent was evaporated under reduced pressure and the residue azeotroped three times with acetonitrile. Purification was by HPLC on a Hichrom ACE column (50×21.2 mm) column eluting with 5-50% acetonitrile in 0.2% aqueous trifluoroacetic acid. The product was dissolved in acetonitrile (10 mL) and treated with a 4M solution of hydrogen chloride in 1,4-dioxane (2 mL). The solvents were evaporated off under reduced pressure and the residue was triturated with diethyl ether to yield the title compound (50 mg).

Workup

  1. customthe solvents were then removed under reduced pressure
  2. customthe residue partitioned between ethyl acetate and saturated aqueous brine
  3. extractionThe aqueous layer was re-extracted with ethyl acetate
  4. customthe combined organic layers were dried
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. dissolutionThe residue was dissolved in trifluoroacetic acid (5 mL)
  8. customthe solvent was evaporated under reduced pressure
  9. customthe residue azeotroped three times with acetonitrile
  10. customPurification
  11. washeluting with 5-50% acetonitrile in 0.2% aqueous trifluoroacetic acid
  12. dissolutionThe product was dissolved in acetonitrile (10 mL)
  13. additiontreated with a 4M solution of hydrogen chloride in 1,4-dioxane (2 mL)
  14. customThe solvents were evaporated off under reduced pressure
  15. customthe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-eb8e4c695b7540409de9fa5df9cc3bc9
Source dataset
uspto-grants-2011_05
Patent number
US07951954B2

Reaction notes

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