Imidazole → HCID 67205868, compound

HRID 2041689Notes

Reaction equation

HRID 2041689 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[N:15]=[N:16][N:17]([CH2:19][CH2:20][OH:21])[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH2:22])[CH2:6][C@@H:5]1[CH3:23])(=[O:3])[CH3:2].N1C=CN=C1.Cl[Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31]>CN(C)C=O>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[N:15]=[N:16][N:17]([CH2:19][CH2:20][O:21][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH2:22])[CH2:6][C@@H:5]1[CH3:23])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 795Imidazole2×HCID 28928tert-Butyldimethylsilyl chloride2×HCID 67206190HCID 67206190, compound

Product 1

HCID 67205868HCID 67205868, compoundYield 54.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 2-{4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]-1H-1,2,3-triazol-1-yl}ethanol (for a preparation see intermediate 45) (358 mg, 0.834 mmol) and imidazole (114 mg, 1.667 mmol) in N,N-dimethylformamide (DMF) (15 mL), was added chloro(1,1-dimethylethyl)dimethylsilane (151 mg, 1.0 mmol) and the resulting reaction mixture was stirred at room temperature for 16 h. Another equivalent of imidazole (114 mg, 1.667 mmol) and chloro(1,1-dimethylethyl)dimethylsilane (151 mg, 1.000 mmol) were then added and after 15 min the resulting mixture was partitioned between EtOAc and water. The layers were separated and the aqueous phase was extracted three times with EtOAc. The combined organic layers were washed twice with brine, dried over MgSO4 and concentrated in vacuovacuo. Purification of the residue on SP4 using a 25 G silica cartridge (gradient:0 to 10% MeOH in DCM) gave (2S,4R)-1-acetyl-6-[1-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-1H-1,2,3-triazol-4-yl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine (202 mg, 0.451 mmol, 54.1% yield) as a yellow oil.

Workup

  1. customthe resulting reaction mixture
  2. customwas partitioned between EtOAc and water
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted three times with EtOAc
  5. washThe combined organic layers were washed twice with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuovacuo
  8. customPurification of the residue on SP4

Sources & evidence

ORD record
ord-8e880d0e6ce24e6e84015f3859f867bb
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

Loading…