Ammonia → HCID 44540228, compound

HRID 1616047Notes

Reaction equation

HRID 1616047 reaction equation
Cl.[N:2]1([C:7]2[CH:12]=[C:11]([C:13]([OH:15])=O)[CH:10]=[CH:9][N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3]1.ClC(N(C)C)=C(C)C.CCN(C(C)C)C(C)C.[NH:33]1[C:41]2[C:36](=[C:37]([C:42]3[CH:43]=[C:44]([NH2:57])[C:45]4[C:49]([CH:50]=3)=[N:48][N:47](C3CCCCO3)[CH:46]=4)[CH:38]=[CH:39][CH:40]=2)[CH:35]=[CH:34]1.CC1C=CC(S(O)(=O)=O)=CC=1.N>C1COCC1>[NH:33]1[C:41]2[C:36](=[C:37]([C:42]3[CH:50]=[C:49]4[C:45]([CH:46]=[N:47][NH:48]4)=[C:44]([NH:57][C:13]([C:11]4[CH:10]=[CH:9][N:8]=[C:7]([N:2]5[CH2:3][CH2:4][CH2:5][CH2:6]5)[CH:12]=4)=[O:15])[CH:43]=3)[CH:38]=[CH:39][CH:40]=2)[CH:35]=[CH:34]1

Participants

8

Reactant 6

HCID 222AmmoniaHCID 6101p-Toluenesulfonic acidHCID 81531DiisopropylethylamineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 45480294HCID 45480294, compoundHCID 582679956-(1H-Indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine

Product 1

HCID 44540228HCID 44540228, compoundYield 12.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-(1-pyrrolidinyl)-4-pyridinecarboxylic acid hydrochloride (38 mg, 0.16 mmol, available from Maybridge) in anhydrous THF (2 ml), was treated with 1-chloro-N,N,2-trimethyl-1-propen-1-amine (0.026 ml, 0.2 mmol, available from Acros) and stirred at room temperature under nitrogen for 2 h. The mixture was then treated with anhydrous DIPEA (0.131 ml, 0.75 mmol) followed by a solution of 6-(1H-indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (50 mg, 0.15 mmol) in THF (2 ml). The mixture was stirred under nitrogen for a further 6 h. Solvents were removed by blow down under a stream of nitrogen and the residue was then dissolved in methanol (3 ml) and evaporated further in a vacuum centrifuge. The residue was then dissolved in methanol (5 ml) then treated with macroporous tosic acid (102 mg, 0.452 mmol) and stirred for 17 h at room temperature. Addition of 0.88 ammonia solution (0.5 ml) was followed by stirring at room temperature for a further 30 mins and then the mixture was separated using a hydrophobic frit. The organic layer was concentrated in vacuo and the residue purified by HPLC (Method E) to afford the title compound (8 mg).

Workup

  1. stirringThe mixture was stirred under nitrogen for a further 6 h
  2. customSolvents were removed by blow down under a stream of nitrogen
  3. dissolutionthe residue was then dissolved in methanol (3 ml)
  4. customevaporated further in a vacuum centrifuge
  5. dissolutionThe residue was then dissolved in methanol (5 ml)
  6. stirringstirred for 17 h at room temperature
  7. stirringby stirring at room temperature for a further 30 mins
  8. customthe mixture was separated
  9. concentrationThe organic layer was concentrated in vacuo
  10. customthe residue purified by HPLC (Method E)

Sources & evidence

ORD record
ord-501ff9fcadb64a79a7b04ac32afb8521
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

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