Iodoethane → methyl 2-(4-(tert-butoxycarbonylamino)-1H-indazol-1-yl)-2-(4-chlorophenyl)butanoate

HRID 1427226Notes

Reaction equation

HRID 1427226 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[N:12][N:13]2[CH:18]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1)[C:19]([O:21][CH3:22])=[O:20])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:30](I)[CH3:31].[H-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[N:12][N:13]2[C:18]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1)([CH2:30][CH3:31])[C:19]([O:21][CH3:22])=[O:20])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 70563540methyl 2-(4-(tert-butoxycarbonylamino)-1H-indazol-1-yl)-2-(4-chlorophenyl)acetate

Product 1

HCID 70562967methyl 2-(4-(tert-butoxycarbonylamino)-1H-indazol-1-yl)-2-(4-chlorophenyl)butanoateYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The compound from step C (1 g, 2.4 mml) and EtI (42 mg, 2.6 mmol) were dissolved in anhydrous DMF (10 mL) Then NaH (144 mg, 3.6 mmol, 60%) was added to the mixture slowly at 0° C. After 30 minutes, the reaction mixture was quenched by saturate NH4Cl (10 mL), extracted with EA, dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column (PE:EA=20:1 to 5:1 to give the title compound (0.608 g, 57%). LC/MS m/z=444.1[M+H]+. The two enantiomers were separated by SFC chiral separation.

Workup

  1. customthe reaction mixture was quenched
  2. concentrationby saturate NH4Cl (10 mL)
  3. extractionextracted with EA
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by silica gel column (PE

Sources & evidence

ORD record
ord-3fb1a3d1838646e79456ea59f3785a97
Source dataset
uspto-grants-2015_01
Patent number
US08933113B2

Reaction notes

Loading…