Benzaldehyde → HCID 69585546, compound

HRID 2188036Notes

Reaction equation

HRID 2188036 reaction equation
[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH2:14][N:13]([C@H:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH3:18])[C@@H:12]([CH2:25][NH2:26])[C:11]=2[S:10][C:9]=1[NH2:27])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:28](=O)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.[BH4-].[Na+].C(N(C(C)C)CC)(C)C.[C:47](Cl)(=[O:49])[CH3:48].C(=O)(O)[O-].[Na+]>C(O)C.ClCCl>[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH2:14][N:13]([C@H:17]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH3:18])[C@@H:12]([CH2:25][N:26]([C:47](=[O:49])[CH3:48])[CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:11]=2[S:10][C:9]=1[NH2:27])=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

9

Reactant 6

HCID 240BenzaldehydeHCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 59091469HCID 59091469, compound

Product 1

HCID 69585546HCID 69585546, compoundYield 46.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 2-amino-7-(S)-aminomethyl-6-(1-(S)-phenyl-ethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester (400 mg, 1.03 mmol) and benzaldehyde (105 mg, 1.03 mmol) was heated to 50° C in ethanol (20 ml) for 1 hour in the presence of molecular sieves (4 A, 7 ml). The reaction mixture was cooled on an ice bath before sodium borohydride (78 mg, 2.06 mmol) was added in three portions over 45 min. The cooling bath was removed and the reaction mixture was allowed to reach room temperature. The mixture was filtered through a plug of Celite and the filter cage was washed with dichloromethane (3×25 ml). The solvent was removed in vacuo and the residue was redissolved in ethyl acetate (50 ml), washed with sodium bicarbonate (50 ml) and dried (MgSO4). The solvent was removed in vacuo before the product was dissolved in dichloromethane (20 ml). The solution was cooled on an ice bath before di-isopropyl-ethyl amine (267 mg, 2.06 mmol) was added followed by drop wise addition of acetyl chloride (81 mg, 1.03 mmol) in dichloromethane (1 ml). The reaction mixture was stirred 1 hour at 0° C. before sodium bicarbonate (20 ml) was added. The mixture was extracted with dichloromethane (2×10 ml) and the combined organic fractions were dried (MgSO4). The crude product was purified by flash column chromatography (petrol ether/ethyl acetate (3:1)), which afforded 250 mg (46%) of 7-(S)-((acetyl-benzyl-amino)methyl)-2-amino-6-(1-(S)-phenyl-ethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester.

Workup

  1. additionwas added in three portions over 45 min
  2. customThe cooling bath was removed
  3. customto reach room temperature
  4. filtrationThe mixture was filtered through a plug of Celite
  5. washthe filter cage was washed with dichloromethane (3×25 ml)
  6. customThe solvent was removed in vacuo
  7. dissolutionthe residue was redissolved in ethyl acetate (50 ml)
  8. washwashed with sodium bicarbonate (50 ml)
  9. dry with materialdried (MgSO4)
  10. customThe solvent was removed in vacuo before the product
  11. dissolutionwas dissolved in dichloromethane (20 ml)
  12. additionwas added
  13. additionwas added
  14. extractionThe mixture was extracted with dichloromethane (2×10 ml)
  15. dry with materialthe combined organic fractions were dried (MgSO4)
  16. customThe crude product was purified by flash column chromatography (petrol ether/ethyl acetate (3:1)), which

Sources & evidence

ORD record
ord-e670d1065ee945f7b6682701eb413522
Source dataset
uspto-grants-2002_06
Patent number
US06410556B1

Reaction notes

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