6-Chloropicolinic acid → HCID 44540963, compound

HRID 1616011Notes

Reaction equation

HRID 1616011 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][CH:3]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CCN(C(C)C)C(C)C.[NH:44]1[C:52]2[C:47](=[C:48]([C:53]3[CH:54]=[C:55]([NH2:62])[C:56]4[CH:57]=[N:58][NH:59][C:60]=4[CH:61]=3)[CH:49]=[CH:50][CH:51]=2)[CH:46]=[CH:45]1>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([NH:62][C:55]2[CH:54]=[C:53]([C:48]3[CH:49]=[CH:50][CH:51]=[C:52]4[C:47]=3[CH:46]=[CH:45][NH:44]4)[CH:61]=[C:60]3[C:56]=2[CH:57]=[N:58][NH:59]3)=[O:10])[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 208126-Chloropicolinic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 582680196-(1H-indol-4-yl)-1H-indazol-4-amine

Product 1

HCID 44540963HCID 44540963, compoundYield 25.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-Chloro-2-pyridinecarboxylic acid (available from Fluorochem, 2540 mg, 16.1 mmol) and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (6130 mg, 16.1 mmol) were dissolved in DMF (40 ml) and DIPEA (8.44 ml) was added. The mixture was stirred at room temperature for 30 mins then 6-(1H-indol-4-yl)-1H-indazol-4-amine (2000 mg, 8.06 mmol) was added and the mixture stirred at room temperature overnight. The reaction mixture was concentrated in vacuo to ˜15 ml which was added to 4×50 g aminopropyl cartridges which had been preconditioned with MeOH. The reaction mixture remained on the cartridges for 3 h before being eluted with MeOH. The fractions were combined and the solvent was removed in vacuo to give a brown oil which was purified by chromatography on silica gel (2×100 g cartridges) eluting with 0-25% MeOH in dichloromethane over 40 mins. Appropriate fractions were combined and the solvent was removed in vacuo to give the title compound (809 mg) as an orange solid.

Workup

  1. stirringthe mixture stirred at room temperature overnight
  2. concentrationThe reaction mixture was concentrated in vacuo to ˜15 ml which
  3. additionwas added to 4×50 g aminopropyl cartridges which
  4. waitThe reaction mixture remained on the cartridges for 3 h
  5. washbefore being eluted with MeOH
  6. customthe solvent was removed in vacuo
  7. customto give a brown oil which
  8. customwas purified by chromatography on silica gel (2×100 g cartridges)
  9. washeluting with 0-25% MeOH in dichloromethane over 40 mins
  10. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-72b5c3f678e344b3b959ba5b742a9ac4
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

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