Potassium Carbonate → 5-(4-methoxypyrimidin-2-yl)-1-methyl-1H-indazole

HRID 879335Notes

Reaction equation

HRID 879335 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][N:3]=1.[CH3:10][N:11]1[C:19]2[C:14](=[CH:15][C:16](B(O)O)=[CH:17][CH:18]=2)[CH:13]=[N:12]1.C([O-])([O-])=O.[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:9][O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:16]2[CH:15]=[C:14]3[C:19](=[CH:18][CH:17]=2)[N:11]([CH3:10])[N:12]=[CH:13]3)[N:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 5889352-Chloro-4-methoxypyrimidineHCID 225589101-Methyl-1H-indazole-5-boronic acid

Product 1

HCID 866998545-(4-methoxypyrimidin-2-yl)-1-methyl-1H-indazole

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
185 °C

Procedure

2-chloro-4-methoxypyrimidine (100.0 mg, 0.69 mmol), 1-methyl-1H-indazol-5-ylboronic acid (133.9 mg, 0.76 mmol), Pd(PPh3)4 (79.9 mg, 0.069 mmol), and K2CO3 (286.8 mg, 2.075 mmol) were taken in a microwave vial and the vial was vacuum pumped and flushed with argon three times. To this mixture was added degassed toluene (2.5 mL) and DMF (0.28 mL). The reaction mixture was heated in a microwave at 185° C. for 30 min, diluted with ethyl acetate, filtered through Celite (ethyl acetate eluent), and concentrated. Purification by flash column chromatography on silica gel (hexanes/ethyl acetate eluent) provided the product. 1H NMR (400 MHz, CDCl3) δ 8.92 (s, 1H), 8.56 (dd, J=8.9, 1.3 Hz, 1H), 8.52 (d, J=5.8 Hz, 1H), 8.10 (s, 1H), 7.47 (d, J=8.9 Hz, 1H), 6.64 (d, J=5.8 Hz, 1H), 4.14 (s, 3H), 4.12 (s, 3H). LCMS-ESI+: calc'd for C13H13N4O: 241.1 (M+H+); Found: 241.2 (M+H+).

Workup

  1. customflushed with argon three times
  2. additionTo this mixture was added
  3. customdegassed toluene (2.5 mL) and DMF (0.28 mL)
  4. additiondiluted with ethyl acetate
  5. filtrationfiltered through Celite (ethyl acetate eluent)
  6. concentrationconcentrated
  7. customPurification by flash column chromatography on silica gel (hexanes/ethyl acetate eluent)
  8. customprovided the product

Sources & evidence

ORD record
ord-41766c839db14fc49f40c742d62dfb49
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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