Imidazole → HCID 68184856, compound

HRID 2041691Notes

Reaction equation

HRID 2041691 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]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:6][C@@H:5]1[CH3:30])(=[O:3])[CH3:2].N1C=CN=C1.Cl[Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38]>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:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:6][C@@H:5]1[CH3:30])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 795Imidazole2×HCID 28928tert-Butyldimethylsilyl chloride2×HCID 68184855HCID 68184855, compound

Product 1

HCID 68184856HCID 68184856, compoundYield 68.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1,1-dimethylethyl {(2S,4R)-1-acetyl-6-[1-(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate (for a preparation see intermediate 47) (659 mg, 1.586 mmol) and imidazole (216 mg, 3.17 mmol) in N,N-dimethylformamide (DMF) (20.0 mL) was treated with chloro(1,1-dimethylethyl)dimethylsilane (0.330 mL, 1.903 mmol) and the resulting reaction mixture was stirred at room temperature for 16 h. Another equivalent of imidazole (216 mg, 3.17 mmol) and chloro(1,1-dimethylethyl)dimethylsilane (0.330 mL, 1.903 mmol) were then added to the reaction which was stirred at room temperature for 1 h then partitioned between water and EtOAc. 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 50 G silica cartridge (gradient:10 to 50% AcOEt in Hexanes) gave 1,1-dimethylethyl {(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-quinolinyl}carbamate (599 mg, 1.085 mmol, 68.4% yield).

Workup

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

Sources & evidence

ORD record
ord-9b37caaeb9404745965e0b33278a62b5
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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