2,4-Dichloropyrimidine → N-(2-chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-1H-indazol-4-amine

HRID 2237411Notes

Reaction equation

HRID 2237411 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[CH3:9][O:10][C:11]1[CH:27]=[CH:26][C:14]([CH2:15][N:16]2[C:24]3[CH:23]=[CH:22][CH:21]=[C:20]([NH2:25])[C:19]=3[CH:18]=[N:17]2)=[CH:13][CH:12]=1.C(N(CC)C(C)C)(C)C>C(O)C>[Cl:1][C:2]1[N:7]=[C:6]([NH:25][C:20]2[C:19]3[CH:18]=[N:17][N:16]([CH2:15][C:14]4[CH:26]=[CH:27][C:11]([O:10][CH3:9])=[CH:12][CH:13]=4)[C:24]=3[CH:23]=[CH:22][CH:21]=2)[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 775312,4-DichloropyrimidineHCID 81531DiisopropylethylamineHCID 685830011-(4-methoxybenzyl)-1H-indazol-4-amine

Product 1

HCID 86626272N-(2-chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-1H-indazol-4-amineYield 64%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 2,4-dichloropyrimidine (3.71 g, 24.87 mmol), 1-(4-methoxybenzyl)-1H-indazol-4-amine (6 g, 23.69 mmol) and N,N-diisopropylethylamine (4.54 mL, 26.06 mmol) in ethanol (60 mL) was stirred at 90° C. for 65 hours. The reaction mixture was concentrated to dryness, diluted with ethyl acetate (100 ml), washed with water (100 ml) and brine (100 ml), dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 5 to 70% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford N-(2-chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-1H-indazol-4-amine (5.53 g, 64%) as a pink solid. NMR Spectrum: (DMSOd6) 3.70 (s, 3H), 5.57 (s, 2H), 6.86 (d, 2H), 6.93 (d, 1H), 7.22 (d, 2H), 7.37 (dd, 1H), 7.48 (d, 1H), 7.59 (d, 1H), 8.22 (d, 1H), 8.23 (s, 1H), 10.13 (s, 1H); Mass spectrum: MH+ 366

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. additiondiluted with ethyl acetate (100 ml)
  3. washwashed with water (100 ml) and brine (100 ml)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography on silica gel eluting with 5 to 70% ethyl acetate in petroleum ether
  7. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-8517fd00930f46279e955b3c80898d3e
Source dataset
uspto-grants-2010_05
Patent number
US07718653B2

Reaction notes

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