Ammonia → N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]pyrazolo[1,5-a]pyridine-2-carboxamide

HRID 42244Notes

Reaction equation

HRID 42244 reaction equation
[N:1]1[N:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]2=[CH:3][C:2]=1[C:10]([OH:12])=O.ClC(N(C)C)=C(C)C.CCN(C(C)C)C(C)C.[NH:30]1[C:38]2[C:33](=[C:34]([C:39]3[CH:40]=[C:41]([NH2:54])[C:42]4[C:46]([CH:47]=3)=[N:45][N:44](C3CCCCO3)[CH:43]=4)[CH:35]=[CH:36][CH:37]=2)[CH:32]=[CH:31]1.CC1C=CC(S(O)(=O)=O)=CC=1.N>C1COCC1.CO>[NH:30]1[C:38]2[C:33](=[C:34]([C:39]3[CH:47]=[C:46]4[C:42]([CH:43]=[N:44][NH:45]4)=[C:41]([NH:54][C:10]([C:2]4[CH:3]=[C:4]5[CH:9]=[CH:8][CH:7]=[CH:6][N:5]5[N:1]=4)=[O:12])[CH:40]=3)[CH:35]=[CH:36][CH:37]=2)[CH:32]=[CH:31]1

Participants

9

Reactant 6

HCID 222AmmoniaHCID 6101p-Toluenesulfonic acidHCID 81531DiisopropylethylamineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 7127820Pyrazolo(1,5-a)pyridine-2-carboxylic acidHCID 582679956-(1H-Indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine

Product 1

HCID 44540219N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]pyrazolo[1,5-a]pyridine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

Pyrazolo[1,5-a]pyridine-2-carboxylic acid (27 mg, 0.166 mmol) was treated with anhydrous THF (2 ml) and then 1-chloro-N,N, 2-trimethylpropenylamine (0.026 ml, 0.20 mmol). The reaction was stirred at room temperature under nitrogen for 2 hrs. The reaction was then treated with anhydrous DIPEA (0.131 ml, 0.753 mmol) and 2 ml of solution of 6-(1H-indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (750 mg, 2.26 mmol) in THF (30 ml). The reaction was then stirred at room temperature under nitrogen for 69 hrs. The solvent was blown-off under a stream of nitrogen, dissolved in methanol (3 ml) and then solvent removed under reduced pressure. The crude reaction mixture was dissolved in methanol (5 ml), treated with Macroporous Tosic Acid (4.45 mmol/g, 102 mg, 0.45 mmol), stirred at room temperature for 17 hrs and then treated with 0.88 ammonia (0.5 ml), stirred for 30 minutes and then filtered. The solvent was removed under reduced pressure and then the residue purified by Mass Directed Automated Preparative HPLC (Method B) to give the title compound.

Workup

  1. stirringThe reaction was then stirred at room temperature under nitrogen for 69 hrs
  2. customsolvent removed under reduced pressure
  3. customThe crude reaction mixture
  4. stirringstirred at room temperature for 17 hrs
  5. stirringstirred for 30 minutes
  6. filtrationfiltered
  7. customThe solvent was removed under reduced pressure
  8. customthe residue purified by Mass Directed Automated Preparative HPLC (Method B)

Sources & evidence

ORD record
ord-66522a60ccb244d8a1260ed17dbad943
Source dataset
uspto-grants-2013_09
Patent number
US08536169B2

Reaction notes

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