6-Methylpyridine-2-carboxylic acid → HCID 44540688, compound

HRID 1616000Notes

Reaction equation

HRID 1616000 reaction equation
[CH3:1][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.[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:6]4[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[N:7]=4)=[O:10])[CH:45]=3)[CH:40]=[CH:41][CH:42]=2)[CH:37]=[CH:36]1

Participants

6

Reactant 3

HCID 702826-Methylpyridine-2-carboxylic 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 44540688HCID 44540688, compoundYield 29.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 81531DiisopropylethylamineSolvent

Procedure

6-Methyl-2-pyridinecarboxylic acid (8 mg, 0.06 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 for 5 mins then left to stand at room temperature overnight. Solvent was removed, 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 (6.6 mg) as a pale brown gum.

Workup

  1. stirringThe reaction mixture was shaken for 5 mins
  2. waitthen left
  3. waitto stand at room temperature overnight
  4. customSolvent was removed
  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-e621f442c5784807904e319a05b73ec3
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

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