Triethylamine → ethyl 2-[1-[4-(6-fluoro-2-naphthamido)benzyl]-1H-indazol-3-yl]acetate

HRID 589386Notes

Reaction equation

HRID 589386 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.[F:31][C:32]1[CH:33]=[C:34]2[C:39](=[CH:40][CH:41]=1)[CH:38]=[C:37]([C:42](Cl)=[O:43])[CH:36]=[CH:35]2.C(=O)(O)[O-].[Na+]>ClCCl>[F:31][C:32]1[CH:33]=[C:34]2[C:39](=[CH:40][CH:41]=1)[CH:38]=[C:37]([C:42]([NH:1][C:2]1[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]=1)=[O:43])[CH:36]=[CH:35]2

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 866748346-Fluoro-2-naphthoyl chlorideHCID 89590263ethyl 2-[1-(4-aminobenzyl)-1H-indazol-3-yl]acetate

Product 1

HCID 89590305ethyl 2-[1-[4-(6-fluoro-2-naphthamido)benzyl]-1H-indazol-3-yl]acetateYield 54.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The crude ethyl 2-[1-(4-aminobenzyl)-1H-indazol-3-yl]acetate (about 1.0 mmol) obtained in the last step and triethylamine (1.4 mL) were dissolved in dichloromethane (15 mL). In an ice bath, dichloromethane solution (10 mL) of the prepared 6-fluoro-2-naphthoyl chloride (about 1.2 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, and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, and filtered. The filtrate was removed under reduced pressure, and the resulting residue was chromatographed on a silica gel column (petroleum ether:ethyl acetate=2:1) to obtain a white solid 262 mg, at a total yield over two steps of reactions of 54.4%.

Workup

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

Sources & evidence

ORD record
ord-9ac9837a09e2413d8071bdc3d72f2609
Source dataset
uspto-grants-2016_01
Patent number
US09233098B2

Reaction notes

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