3-Methylpicolinic acid → HCID 44540590, compound

HRID 1615999Notes

Reaction equation

HRID 1615999 reaction equation
[CH3:1][C:2]1[C:3]([C:8]([OH:10])=O)=[N:4][CH:5]=[CH:6][CH:7]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[NH:35]1[C:43]2[C:38](=[C:39]([C:44]3[CH:45]=[C:46]([NH2:59])[C:47]4[C:51]([CH:52]=3)=[N:50][N:49](C3CCCCO3)[CH:48]=4)[CH:40]=[CH:41][CH:42]=2)[CH:37]=[CH:36]1>CN(C=O)C.CCN(C(C)C)C(C)C>[NH:35]1[C:43]2[C:38](=[C:39]([C:44]3[CH:52]=[C:51]4[C:47]([CH:48]=[N:49][NH:50]4)=[C:46]([NH:59][C:8]([C:3]4[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=4)=[O:10])[CH:45]=3)[CH:40]=[CH:41][CH:42]=2)[CH:37]=[CH:36]1

Participants

6

Reactant 3

HCID 2687573-Methylpicolinic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 582679956-(1H-Indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine

Product 1

HCID 44540590HCID 44540590, compoundYield 24.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 81531DiisopropylethylamineSolvent

Procedure

3-Methyl-2-pyridinecarboxylic acid (11 mg, 0.08 mmol) in DMF (0.20 ml) was treated with O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (27 mg, 0.07 mmol) in DMF (0.20 ml) and DIPEA (0.030 ml). The reaction mixture was shaken for five minutes then treated with 6-(1H-Indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (20 mg, 0.06 mmol) in DMF (0.20 ml). The reaction mixture was shaken then left to stand at room temperature overnight. Solvent was removed in vacuo and the product re-dissolved in methanol (1 ml) then applied to an SCX cartridge (1 g) which had been pre-rinsed with methanol. After 1 h, the cartridge was eluted with ammonia in methanol (2M, 2×3 ml). Fractions containing product were combined, dried and then further purified by Mass Directed Automated Preparative HPLC (Method D). Fractions containing product were combined and dried to give the title compound (5.5 mg) as a pale yellow gum.

Workup

  1. stirringThe reaction mixture was shaken
  2. waitthen left
  3. waitto stand at room temperature overnight
  4. customSolvent was removed in vacuo
  5. dissolutionthe product re-dissolved in methanol (1 ml)
  6. washhad been pre-rinsed with methanol
  7. waitAfter 1 h
  8. washthe cartridge was eluted with ammonia in methanol (2M, 2×3 ml)
  9. additionFractions containing product
  10. customdried
  11. customfurther purified by Mass Directed Automated Preparative HPLC (Method D)
  12. additionFractions containing product
  13. customdried

Sources & evidence

ORD record
ord-8b439d5d36d24256b258b8cb61f48f9e
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

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