Acetyl chloride → HCID 22083379, compound

HRID 2188035Notes

Reaction equation

HRID 2188035 reaction equation
C([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])(C)(C)C.[O:28]([C:35]1[CH:42]=[CH:41][C:38]([CH:39]=O)=[CH:37][CH:36]=1)[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:54](Cl)(=[O:56])[CH3:55]>C(O)C.ClCCl>[C:54]([N:26]([CH2:25][C@H:12]1[C:11]2[S:10][C:9]([NH2:27])=[C:8]([C:6]([OH:5])=[O:7])[C:16]=2[CH2:15][CH2:14][N:13]1[C@H:17]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[CH3:18])[CH2:39][C:38]1[CH:41]=[CH:42][C:35]([O:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:36][CH:37]=1)(=[O:56])[CH3:55]

Participants

8

Reactant 5

HCID 6367Acetyl chlorideHCID 661394-PhenoxybenzaldehydeHCID 81531DiisopropylethylamineHCID 4311764Sodium borohydrideHCID 59091469HCID 59091469, compound

Product 1

HCID 22083379HCID 22083379, compoundYield 44.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

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 (500 mg, 1.29 mmol) and 4-phenoxybenzaldehyde (256 mg, 1.29 mmol) was heated to 50° C. in ethanol (50 ml) for 1 hour in the presence of molecular sieves (4 A, 5 ml). The reaction mixture was cooled on an ice bath before sodium borohydride (98 mg, 2.59 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 (10 ml). The solution was cooled on an ice bath before di-isopropyl-ethyl amine (101 mg, 1.29 mmol) was added followed by drop wise addition of acetyl chloride (101 mg, 1.29 mmol) in dichloromethane (1 ml). The reaction mixture was stirred 1 hour at 0° C. and the solution was washed with sodium bicarbonate (10 ml) and dried (MgSO4). The crude product was purified by flash column chromatography (SiO2, ethyl acetate-petrol ether 1:3) to give 320 mg (41%) of 7-(S)-((acetyl-(4-phenoxy-benzyl)amino)methyl)-2-amino-6-(1-(S)-phenyl-ethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid

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 (10 ml)
  12. additionwas added
  13. washthe solution was washed with sodium bicarbonate (10 ml)
  14. dry with materialdried (MgSO4)
  15. customThe crude product was purified by flash column chromatography (SiO2, ethyl acetate-petrol ether 1:3)

Sources & evidence

ORD record
ord-f502371e21c548e98c9d032f0b5a7fa9
Source dataset
uspto-grants-2002_06
Patent number
US06410556B1

Reaction notes

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