2,6-Dichlorobenzoyl chloride → HCID 68159440, compound

HRID 508198Notes

Reaction equation

HRID 508198 reaction equation
[CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][N:8]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[NH:21][N:20]=4)=[CH:15][CH:14]=3)=[N:11][N:10]=[N:9]2)=[CH:5][CH:4]=1.CC([O-])(C)C.[K+].[Cl:36][C:37]1[CH:45]=[CH:44][CH:43]=[C:42]([Cl:46])[C:38]=1[C:39](Cl)=[O:40]>C1COCC1>[Cl:36][C:37]1[CH:45]=[CH:44][CH:43]=[C:42]([Cl:46])[C:38]=1[C:39]([N:21]1[C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:19]([C:16]2[CH:15]=[CH:14][C:13]([C:12]3[N:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:29][CH:28]=4)[N:9]=[N:10][N:11]=3)=[CH:18][CH:17]=2)=[N:20]1)=[O:40]

Participants

5

Reactant 3

HCID 783922,6-Dichlorobenzoyl chlorideHCID 23665647Potassium tert-butoxideHCID 68159279HCID 68159279, compound

Product 1

HCID 68159440HCID 68159440, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of a mixture of regio-isomers of 3-(4-(1-(4-Methoxybenzyl)-1H-tetrazol-5-yl)phenyl)-1H-indazole (Example 20, step i) (50 mg, 0.13 mmol) was dissolved in anhydrous THF (1 ml). After addition of t-BuOK (16 mg, 0.14 mmol,) the reaction mixture was stirred at room temperature for 15 min. Subsequently, 2,6-dichlorobenzoyl chloride (21 μl, 0.14 mmol) was added and the reaction mixture was stirred for another 2 h at room temperature. The solvent was evaporated under reduced pressure, the residue was dissolved in dichloromethane and washed with water, an aqueous solution of 5% K2CO3 and water. The organic solvent was evaporated under reduced pressure and the residue was dried in vacuo. The product was purified by preparative HPLC to afford (2,6-dichlorophenyl)(3-(4-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)phenyl)-1H-indazol-1-yl)methanone as a mixture of 2 regioisomers in a 98 to 2 ratio (59 mg, 74%).

Workup

  1. stirringthe reaction mixture was stirred for another 2 h at room temperature
  2. customThe solvent was evaporated under reduced pressure
  3. dissolutionthe residue was dissolved in dichloromethane
  4. washwashed with water
  5. customThe organic solvent was evaporated under reduced pressure
  6. customthe residue was dried in vacuo
  7. customThe product was purified by preparative HPLC

Sources & evidence

ORD record
ord-1bc1d943f81b4fe88c53c2be6d76a2ea
Source dataset
uspto-grants-2015_08
Patent number
US09095583B2

Reaction notes

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