Triethylamine → 2-{[(3-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-(methyloxy)-1H-indazol-1-yl]methyl}phenyl)methyl]amino}-1,1-dimethyl-2-oxoethyl acetate

HRID 1808568Notes

Reaction equation

HRID 1808568 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([CH2:9][N:10]2[C:18]3[C:13](=[C:14]([O:19][CH3:20])[CH:15]=[CH:16][CH:17]=3)[C:12]([NH:21][S:22]([C:25]3[S:26][C:27]([Cl:30])=[CH:28][CH:29]=3)(=[O:24])=[O:23])=[N:11]2)[CH:6]=[CH:7][CH:8]=1.C(N(CC)CC)C.[C:38]([O:41][C:42]([CH3:47])([CH3:46])[C:43](Cl)=[O:44])(=[O:40])[CH3:39]>ClCCl>[C:38]([O:41][C:42]([CH3:47])([CH3:46])[C:43]([NH:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][N:10]2[C:18]3[C:13](=[C:14]([O:19][CH3:20])[CH:15]=[CH:16][CH:17]=3)[C:12]([NH:21][S:22]([C:25]3[S:26][C:27]([Cl:30])=[CH:28][CH:29]=3)(=[O:24])=[O:23])=[N:11]2)[CH:4]=1)=[O:44])(=[O:40])[CH3:39]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1234962-Acetoxyisobutyroyl chlorideHCID 59455974HCID 59455974, compound

Product 1

HCID 580545882-{[(3-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-(methyloxy)-1H-indazol-1-yl]methyl}phenyl)methyl]amino}-1,1-dimethyl-2-oxoethyl acetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A stirring suspension of N-[1-{[3-(aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide (40.5 g, 87 mmol) in dichloromethane (1000 mL) and triethylamine (36.4 mL, 262 mmol) was cooled down and then 2-chloro-1,1-dimethyl-2-oxoethyl acetate (12.52 mL, 87 mmol) was added dropwise. The reaction mixture was stirred at room temperature under nitrogen for 1 h and 20 min. It was then washed with 2M HCl (300 ml), NaHCO3 solution (300 ml), brine, dried over magnesium sulphate and filtered. The filtrate was evaporated in vacuo to give a white solid. The residue was dissolved in DCM and loaded onto a 1500 g silica column and eluted with 40-100% ethyl acetate in cyclohexane over 8 CV. The required fractions were combined and evaporated in vacuo to give the title compound in two batches (37.87 g, 73%) and (3.39 g) as white foams. HPLC showed that the latter batch was not pure, therefore it was purified again on a 120 g silica column using a gradient of 40-75% ethyl acetate in cyclohexane over 8 CV.

Workup

  1. temperaturewas cooled down
  2. washIt was then washed with 2M HCl (300 ml), NaHCO3 solution (300 ml), brine
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. customThe filtrate was evaporated in vacuo
  6. customto give a white solid
  7. washeluted with 40-100% ethyl acetate in cyclohexane over 8 CV
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-0bcb77f5e25d495e9c3cfbb52ee9fa20
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

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