Ammonia → HCID 44540785, compound

HRID 1616008Notes

Reaction equation

HRID 1616008 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[CH:11]=[C:12]([NH2:25])[C:13]4[C:17]([CH:18]=3)=[N:16][N:15](C3CCCCO3)[CH:14]=4)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[N:50]1[CH:55]=[CH:54][CH:53]=[C:52]([C:56](O)=[O:57])[CH:51]=1.CCN(C(C)C)C(C)C.C1(C)C=CC(S(O)(=O)=O)=CC=1.N>CN(C=O)C>[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[CH:18]=[C:17]4[C:13]([CH:14]=[N:15][NH:16]4)=[C:12]([NH:25][C:56]([C:52]4[CH:51]=[N:50][CH:55]=[CH:54][CH:53]=4)=[O:57])[CH:11]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

8

Reactant 6

HCID 222AmmoniaHCID 938Nicotinic AcidHCID 6101p-Toluenesulfonic acidHCID 81531DiisopropylethylamineHCID 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 44540785HCID 44540785, compoundYield 41.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 6-(1H-indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (50 mg, 0.15 mmol), O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (63 mg, 0.17 mmol) and 3-pyridinecarboxylic acid (20 mg, 0.16 mmol) was treated with DMF (2 ml) and DIPEA (0.052 ml). The reaction was stirred at room temperature for approximately 67.5 hours, then the solvent was removed in vacuo and the residue dissolved in methanol (3 ml). This was treated with macroporous p-toluenesulfonic acid resin (loading 1.43 mmol/g, 316 mg, 0.45 mmol), stirred for approximately 2 hours and then overnight, then treated with ammonia solution (0.88, 0.30 ml). The mixture was stirred for 5 mins, then the resin was filtered and the filtrate evaporated (blown down). The residue was purified by Mass Directed Automated Preparative HPLC (Method B). One fraction was evaporated to give the title compound (22 mg) as a yellow solid.

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionthe residue dissolved in methanol (3 ml)
  3. stirringstirred for approximately 2 hours
  4. stirringThe mixture was stirred for 5 mins
  5. filtrationthe resin was filtered
  6. customthe filtrate evaporated (
  7. customThe residue was purified by Mass Directed Automated Preparative HPLC (Method B)
  8. customOne fraction was evaporated

Sources & evidence

ORD record
ord-da9d85f46a6a4a55a0a488b5af72f350
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

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