Triethylamine → ethyl 2-[1-[4-(4-chlorobenzamido)benzyl]-1H-indazol-3-yl]acetate

HRID 589369Notes

Reaction equation

HRID 589369 reaction equation
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[N:8]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[Cl:31][C:32]1[CH:40]=[CH:39][C:35]([C:36](Cl)=[O:37])=[CH:34][CH:33]=1.C(=O)(O)[O-].[Na+]>ClCCl>[Cl:31][C:32]1[CH:40]=[CH:39][C:35]([C:36]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:6][N:7]3[C:15]4[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=4)[C:9]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[N:8]3)=[CH:22][CH:23]=2)=[O:37])=[CH:34][CH:33]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 85014-Chlorobenzoyl chlorideHCID 516892Sodium BicarbonateHCID 89590263ethyl 2-[1-(4-aminobenzyl)-1H-indazol-3-yl]acetate

Product 1

HCID 89590262ethyl 2-[1-[4-(4-chlorobenzamido)benzyl]-1H-indazol-3-yl]acetateYield 53.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The crude ethyl 2-[1-(4-aminobenzyl)-1H-indazol-3-yl]acetate (about 0.663 mmol) obtained in the last step and triethylamine (1.0 mL) were dissolved in dichloromethane (15 mL). In an ice bath, a dichloromethane solution (10 mL) of 4-chlorobenzoyl chloride (117 mg, 0.669 mmol) was added dropwise slowly. Upon completion of the dropwise addition, it was reacted at room temperature for 16 hours. An aqueous solution of sodium bicarbonate was added to quench. It was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, and filtered. The filtrate was rotate evaporated. The resulting residue was chromatographed on a silica gel column (petroleum ether:ethyl acetate=2:1) to obtain a white solid 159 mg, at a total yield over two steps of reactions of 53.5%.

Workup

  1. additionUpon completion of the dropwise addition, it
  2. customwas reacted at room temperature for 16 hours
  3. customto quench
  4. extractionIt was extracted with ethyl acetate
  5. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customThe resulting residue was chromatographed on a silica gel column (petroleum ether:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-718c27fc81c34ed4a27276ed7c61073d
Source dataset
uspto-grants-2016_01
Patent number
US09233098B2

Reaction notes

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