Heptane → 7-(2,4-dichloro-phenyl)-2-methyl-2H-indazole-3-carboxylic acid cyclopropylmethyl-propyl-amide
Reaction equation
[CH2:1]([NH:4][CH2:5][CH:6]1[CH2:8][CH2:7]1)[CH2:2][CH3:3].C[Al](C)C.CCCCCCC.CO[C:22]([C:24]1[N:25]([CH3:41])[N:26]=[C:27]2[C:32]=1[CH:31]=[CH:30][CH:29]=[C:28]2[C:33]1[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:34]=1[Cl:40])=[O:23].[OH-].[Na+]>C1C=CC=CC=1>[CH:6]1([CH2:5][N:4]([CH2:1][CH2:2][CH3:3])[C:22]([C:24]2[N:25]([CH3:41])[N:26]=[C:27]3[C:32]=2[CH:31]=[CH:30][CH:29]=[C:28]3[C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:34]=2[Cl:40])=[O:23])[CH2:8][CH2:7]1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 79 °C
Procedure
To a solution of N-propylcyclopropanemethyl amine (0.69 mL, 4.8 mmol) in 12 mL of benzene was slowly added a 2M solution of trimethylaluminum in heptane (2.4 mL, 4.8 mmol), and the solution was stirred for 75 m. The solution was transferred with a pipette to a solution of 35b (0.200 g, 0.597 mmol) in 10 mL of benzene. The solution was heated to 79° C., stirred for 2 d, then cooled to 0-5° C. A 2 M aqueous NaOH solution (20 mL) was slowly added, and the mixture was extracted with three 20 mL portions of dichloromethane. The combined organic layers were washed with 40 mL of a saturated NaCl solution, dried over MgSO4, filtered, and concentrated to a brown oil. Column chromatography (0→20% EtOAc/hexanes) afforded 7-(2,4-dichloro-phenyl)-2-methyl-2H-indazole-3-carboxylic acid cyclopropylmethyl-propyl-amide (35c: 0.117 g; 47%) as an oil.
Workup
- stirringstirred for 2 d
- temperaturecooled to 0-5° C
- extractionthe mixture was extracted with three 20 mL portions of dichloromethane
- washThe combined organic layers were washed with 40 mL of a saturated NaCl solution
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated to a brown oil
Sources & evidence
- ORD record
- ord-5a8c0f923b064af98a26f4fae8b7d75f
- Source dataset
- uspto-grants-2008_04
- Patent number
- US07365211B2
Reaction notes
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