2-Amino-4-chloro-6-methylpyrimidine → 4-(6-bromo-3-methyl-1H-indazol-1-yl)-6-methylpyrimidin-2-amine

HRID 1398625Notes

Reaction equation

HRID 1398625 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:11])=[N:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:15]1[CH:20]=[C:19]([CH3:21])[N:18]=[C:17]([NH2:22])[N:16]=1>CN(C=O)C.C(#N)C>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:11])=[N:7][N:8]2[C:15]2[CH:20]=[C:19]([CH3:21])[N:18]=[C:17]([NH2:22])[N:16]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 218102-Amino-4-chloro-6-methylpyrimidineHCID 24758Sodium hydrideHCID 178434209HCID 178434209, compound

Product 1

HCID 681815734-(6-bromo-3-methyl-1H-indazol-1-yl)-6-methylpyrimidin-2-amine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 6-bromo-3-methyl-1H-indazole (500 mg, 2.37 mmol) in dry DMF (5 mL) at 0° C. under an atmosphere of nitrogen was introduced sodium hydride (684 mg of a 60% dispersion in mineral oil, 7.11 mmol). After warming to RT for 30 minutes, 4-chloro-6-methylpyrimidin-2-amine (510 mg, 3.55 mmol) was added and the solution warmed to 65° C. for 18 hr. The reaction mixture was cooled to RT, quenched by dropwise addition of water (5 mL) and extracted with 2:1 chloroform/isopropanol (3×10 mL extractions). The combined organic extracts were washed with water (5 mL) and brine (5 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by column chromatography (Biotage, DCM containing a 0-10% gradient of methanol) furnished a yellow semi-solid which was slurried in acetonitrile (3 mL). The precipitate was collected by filtration to furnish the title compound as a yellow solid: 1H NMR (500 MHz, DMSO) delta 2.29 (3H, s), 2.56 (3H, s), 6.79-6.93 (2H, m), 6.93-6.95 (1H, m), 7.48 (1H, dd, J=8.43, 1.66 Hz), 7.78 (1H, d, J=8.35 Hz), 9.07 (1H, d, J=1.42 Hz); LC-MS: m/z=+317.95/319.95.

Workup

  1. temperaturethe solution warmed to 65° C. for 18 hr
  2. temperatureThe reaction mixture was cooled to RT
  3. customquenched by dropwise addition of water (5 mL)
  4. extractionextracted with 2:1 chloroform/isopropanol (3×10 mL extractions)
  5. washThe combined organic extracts were washed with water (5 mL) and brine (5 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by column chromatography (Biotage, DCM containing a 0-10% gradient of methanol)
  10. customfurnished a yellow semi-solid which
  11. filtrationThe precipitate was collected by filtration

Sources & evidence

ORD record
ord-27f500ae5a974309932397b5dd99fdf1
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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