Tetrahydrofuran → 4-methyl-1-(2-(1-methyl-1H-indazol-5-ylamino)pyrimidin-4-yl)-1H-pyrrole-3-carbaldehyde

HRID 539902Notes

Reaction equation

HRID 539902 reaction equation
[CH3:1][C:2]1[C:6]([CH:7]=[O:8])=[CH:5][NH:4]N=1.[CH3:9][N:10]1[C:18]2[C:13](=[CH:14][C:15]([NH:19][C:20]3[N:25]=[C:24](S(C)(=O)=O)[CH:23]=[CH:22][N:21]=3)=[CH:16][CH:17]=2)[CH:12]=[N:11]1.[H-].[Na+].[CH2:32]1COCC1>>[CH3:1][C:2]1[C:6]([CH:7]=[O:8])=[CH:5][N:4]([C:24]2[CH:23]=[CH:22][N:21]=[C:20]([NH:19][C:15]3[CH:14]=[C:13]4[C:18](=[CH:17][CH:16]=3)[N:10]([CH3:9])[N:11]=[CH:12]4)[N:25]=2)[CH:32]=1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 866989931-methyl-N-(4-(methylsulfonyl)pyrimidin-2-yl)-1H-indazol-5-amine2×HCID 1784345503-methyl-1H-pyrazole-4-carbaldehyde

Product 1

HCID 866989924-methyl-1-(2-(1-methyl-1H-indazol-5-ylamino)pyrimidin-4-yl)-1H-pyrrole-3-carbaldehydeYield 66%

Procedure

To a solution of 3-methyl-1H-pyrazole-4-carbaldehyde, intermediate 12 (0.33 g, 3.0 mmol) in 10 mL of THF was added 0.12 g of 60% sodium hydride with ice bath cooling and then it was stirred for 20 minute at the same temperature. To this, was added of 10 mL solution of 1-methyl-N-(4-(methansulfonyl)pyrimidin-2-yl)-1H-indazol-5-amine (0.6 g, 2.0 mmol) in THF. The reaction was allowed to warm up to room temperature and then stirred for 2 hours at rt. The reaction was quenched with water, extracted with dichloromethane (×2) and washed with brine. The collected organic layers were dried over anhydrous sodium sulfate and then concentrated in vacuo. The resulting residue was solidified with heptane and then collected by filtration to afford the desired intermediate 13 as a white solid (0.45 g, 66%).

Workup

  1. temperaturecooling
  2. stirringstirred for 2 hours at rt
  3. customThe reaction was quenched with water
  4. extractionextracted with dichloromethane (×2)
  5. washwashed with brine
  6. dry with materialThe collected organic layers were dried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. filtrationcollected by filtration

Sources & evidence

ORD record
ord-160bc66f1f5e47c18bb3fcae70a9e27a
Source dataset
uspto-grants-2014_10
Patent number
US08871778B2

Reaction notes

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