Sodium hydride → 1-[2-amino-6-(methylamino)pyrimidin-4-yl]-6-iodo-N,N-dimethyl-1H-indazole-3-carboxamide

HRID 1398623Notes

Reaction equation

HRID 1398623 reaction equation
[I:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([N:13]([CH3:15])[CH3:14])=[O:12])=[N:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:19]1[N:24]=[C:23]([NH2:25])[N:22]=[C:21]([NH:26][CH3:27])[CH:20]=1>CN(C=O)C>[NH2:25][C:23]1[N:24]=[C:19]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([I:1])[CH:10]=3)[C:6]([C:11]([N:13]([CH3:15])[CH3:14])=[O:12])=[N:7]2)[CH:20]=[C:21]([NH:26][CH3:27])[N:22]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2354466-Chloro-n4-methylpyrimidine-2,4-diamineHCID 681817976-iodo-N,N-dimethyl-1H-indazole-3-carboxamide

Product 1

HCID 681818081-[2-amino-6-(methylamino)pyrimidin-4-yl]-6-iodo-N,N-dimethyl-1H-indazole-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
180 °C

Procedure

To a suspension of 6-iodo-N,N-dimethyl-1H-indazole-3-carboxamide (100 mg, 0.32 mmol) at 0° C. in DMF (3 mL) was added sodium hydride (19 mg of a 60% dispersion in mineral oil, 0.47 mmol). The reaction mixture was allowed to warm to RT over 15 minutes before the addition of 6-chloro-4-N-methylpyrimidine-2,4-diamine (75 mg, 0.47 mmol). The reaction mixture was then heated at 180° C. for 2 hr. The reaction mixture was allowed to cool to RT. The mixture was cooled to 0° C. and quenched by addition of water (1 mL) and the volatiles evaporated in vacuo. The mixture was diluted with sat ammonium chloride (20 mL) and extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried (Na2SO4), filtered and evaporated in vacuo. Purification of the residue by column chromatography (Biotage, 55-100% ethyl acetate: heptanes) gave the title compound: 1H NMR (500 MHz, DMSO) delta 2.78 (3H, s), 3.08 (3H, s), 3.42 (3H, s), 6.24 (1H, s), 6.48 (2H, s), 7.08 (1H, s), 7.64 (1H, m), 7.79 (1H, m), 9.40 (1H, s); LC-MS: m/z=+438.0 (M+H)+.

Workup

  1. temperatureto cool to RT
  2. temperatureThe mixture was cooled to 0° C.
  3. customquenched by addition of water (1 mL)
  4. customthe volatiles evaporated in vacuo
  5. additionThe mixture was diluted with sat ammonium chloride (20 mL)
  6. extractionextracted with ethyl acetate (3×50 mL)
  7. dry with materialThe combined organic extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customPurification of the residue by column chromatography (Biotage, 55-100% ethyl acetate: heptanes)

Sources & evidence

ORD record
ord-13cdee7a7a44458ea1fa131f36ef9a67
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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