Methyl iodide → N-(2-chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-N-methyl-1H-indazol-4-amine

HRID 2237412Notes

Reaction equation

HRID 2237412 reaction equation
CI.[Cl:3][C:4]1[N:9]=[C:8]([NH:10][C:11]2[C:12]3[CH:13]=[N:14][N:15]([CH2:20][C:21]4[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=4)[C:16]=3[CH:17]=[CH:18][CH:19]=2)[CH:7]=[CH:6][N:5]=1.[C:29](=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:3][C:4]1[N:9]=[C:8]([N:10]([CH3:29])[C:11]2[C:12]3[CH:13]=[N:14][N:15]([CH2:20][C:21]4[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=4)[C:16]=3[CH:17]=[CH:18][CH:19]=2)[CH:7]=[CH:6][N:5]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 86626272N-(2-chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-1H-indazol-4-amine

Product 1

HCID 86626273N-(2-chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-N-methyl-1H-indazol-4-amineYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Methyl iodide (1.021 mL, 16.40 mmol) was added dropwise to a stirred suspension of N-(2-chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-1H-indazol-4-amine (4 g, 10.93 mmol, Example 3 starting material) and potassium carbonate (2.267 g, 16.40 mmol) in DMF (40 mL) at 0° C. under nitrogen. The resulting suspension was stirred at 0° C. for 15 minutes and was allowed to warm to room temperature. The reaction mixture was stirred at room temperature overnight, filtered off and washed with ethyl acetate. The filtrate was concentrated to dryness, diluted with dichloromethane (40 ml), washed with water (40 ml), brine (40 ml), dried over magnesium sulfate and concentrated. The residue was purified by flash chromatography on silica gel eluting with 0 to 45% ethyl acetate in petroleum ether to afford N-(2-chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-N-methyl-1H-indazol-4-amine (3.4 g, 82%) as a pale orange solid. NMR Spectrum: (DMSOd6) 3.50 (s, 3H), 3.71 (s, 3H), 5.63 (s, 2H), 6.19 (d, 1H), 6.89 (d, 2H), 7.16 (d, 1H), 7.29 (d, 2H), 7.49 (dd, 1H), 7.81 (d, 1H), 7.96 (d, 1H), 8.00 (s, 1H); Mass spectrum: MH+ 380.

Workup

  1. temperatureto warm to room temperature
  2. stirringThe reaction mixture was stirred at room temperature overnight
  3. filtrationfiltered off
  4. washwashed with ethyl acetate
  5. concentrationThe filtrate was concentrated to dryness
  6. additiondiluted with dichloromethane (40 ml)
  7. washwashed with water (40 ml), brine (40 ml)
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography on silica gel eluting with 0 to 45% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-051753c84f8448778ccb5b92eb9b77e0
Source dataset
uspto-grants-2010_05
Patent number
US07718653B2

Reaction notes

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