Diisopropylethylamine → N-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-6-(1-piperidinylmethyl)-2-pyridinecarboxamide

HRID 1616006Notes

Reaction equation

HRID 1616006 reaction equation
[N:1]1([CH2:7][C:8]2[N:13]=[C:12]([C:14]([OH:16])=O)[CH:11]=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]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:50]1[C:58]2[C:53](=[C:54]([C:59]3[CH:60]=[C:61]([NH2:74])[C:62]4[C:66]([CH:67]=3)=[N:65][N:64](C3CCCCO3)[CH:63]=4)[CH:55]=[CH:56][CH:57]=2)[CH:52]=[CH:51]1.C(=O)(O)[O-].[Na+]>CN(C=O)C>[NH:50]1[C:58]2[C:53](=[C:54]([C:59]3[CH:67]=[C:66]4[C:62]([CH:63]=[N:64][NH:65]4)=[C:61]([NH:74][C:14]([C:12]4[CH:11]=[CH:10][CH:9]=[C:8]([CH2:7][N:1]5[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]5)[N:13]=4)=[O:16])[CH:60]=3)[CH:55]=[CH:56][CH:57]=2)[CH:52]=[CH:51]1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58267993HCID 58267993, compoundHCID 582679956-(1H-Indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine

Product 1

HCID 44540784N-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-6-(1-piperidinylmethyl)-2-pyridinecarboxamideYield 37.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-(1-piperidinylmethyl)-2-pyridinecarboxylic acid (33 mg, 0.15 mmol) in DMF (0.6 ml) was added O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (57 mg, 0.15 mmol) and DIPEA (0.052 ml) and the mixture was stirred for 5 mins at room temperature. 6-(1H-Indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (33 mg, 0.10 mmol) was added and the mixture was stirred for 3 h and then overnight. The mixture was then treated with saturated sodium bicarbonate solution (10 ml) and extracted with dichloromethane (3×10 ml). The extracts were passed through a hydrophobic frit and blown to dryness under a stream of nitrogen. The crude product was dissolved in methanol (2 ml) and hydrochloric acid (5M, 2-3 drops) were added. The solution was shaken for 2 h then blown to dryness under a stream of nitrogen then purified by Mass Directed Automated Preparative HPLC (Method B) to give the title compound (17 mg).

Workup

  1. stirringthe mixture was stirred for 3 h
  2. customovernight
  3. extractionextracted with dichloromethane (3×10 ml)
  4. dissolutionThe crude product was dissolved in methanol (2 ml)
  5. additionhydrochloric acid (5M, 2-3 drops) were added
  6. stirringThe solution was shaken for 2 h
  7. customthen purified by Mass Directed Automated Preparative HPLC (Method B)

Sources & evidence

ORD record
ord-8ed298b8badc411f870e7b2f237277a6
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

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