Water → N-[6-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-1-(1-methylethyl)-1H-pyrazole-5-carboxamide

HRID 1695720Notes

Reaction equation

HRID 1695720 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH2:17])[C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[CH:6]=2.CCN(C(C)C)C(C)C.[CH3:27][CH:28]([N:30]1[C:34]([C:35](Cl)=[O:36])=[CH:33][CH:32]=[N:31]1)[CH3:29].O>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([NH:17][C:35]([C:34]2[N:30]([CH:28]([CH3:29])[CH3:27])[N:31]=[CH:32][CH:33]=2)=[O:36])[C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[CH:6]=2

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 582557836-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine2×HCID 583564221-Isopropyl-1H-pyrazole-5-carbonyl chloride

Product 1

HCID 58255796N-[6-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-1-(1-methylethyl)-1H-pyrazole-5-carboxamideYield 85.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

6-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (2.25 g, 7.59 mmol) was dissolved in DCM (40 ml) and DIPEA (2.85 ml, 16.34 mmol) was added. 1-(1-methylethyl)-1H-pyrazole-5-carbonyl chloride (1.41 g, 8.17 mmol) in DCM (10 ml) was added and the mixture left to stir at room temperature overnight. Water (50 ml) was added and the mixture vigorously stirred. The DCM layer was passed through a hydrophobic frit and evaporated to dryness. The material was combined with that obtained from a previous smaller scale reaction carried out in an identical manner but starting with 6-bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (0.2 g, 0.675 mmol). The combined crude materials were purified by chromatography on silica using a 50 g cartridge and eluting progressively with DCM, then 1-4% methanol in DCM. Product containing fractions were combined and evaporated to dryness to afford the title compound (2.8 g).

Workup

  1. waitthe mixture left
  2. stirringthe mixture vigorously stirred
  3. customevaporated to dryness
  4. customthat obtained from a previous smaller scale reaction
  5. customwere purified by chromatography on silica using a 50 g cartridge
  6. washeluting progressively with DCM
  7. additionProduct containing fractions
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-dc4b1e30e7284d57a735f0213be4e9af
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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