Hydrochloric Acid → N-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-2-(3-methyl-1H-pyrazol-1-yl)acetamide

HRID 42248Notes

Reaction equation

HRID 42248 reaction equation
[CH3:1][C:2]1[CH:6]=[CH:5][N:4]([CH2:7][C:8]([OH:10])=O)[N:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH:44]1[C:52]2[C:47](=[C:48]([C:53]3[CH:54]=[C:55]([NH2:68])[C:56]4[CH:57]=[N:58][N:59](C5CCCCO5)[C:60]=4[CH:61]=3)[CH:49]=[CH:50][CH:51]=2)[CH:46]=[CH:45]1.Cl>CN(C=O)C.CO>[NH:44]1[C:52]2[C:47](=[C:48]([C:53]3[CH:61]=[C:60]4[C:56]([CH:57]=[N:58][NH:59]4)=[C:55]([NH:68][C:8](=[O:10])[CH2:7][N:4]4[CH:5]=[CH:6][C:2]([CH3:1])=[N:3]4)[CH:54]=3)[CH:49]=[CH:50][CH:51]=2)[CH:46]=[CH:45]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531Diisopropylethylamine2×HCID 50123292-(3-methyl-1H-pyrazol-1-yl)acetic acid2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 673022286-(1H-Indol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine

Product 1

HCID 44540308N-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-2-(3-methyl-1H-pyrazol-1-yl)acetamideYield 31%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×

Procedure

(3-Methyl-1H-pyrazol-1-yl)acetic acid (38 mg, 0.27 mmol) (from Art-Chem GmbH), HATU (126 mg, 0.33 mmol) and DIPEA (0.158 ml, 0.91 mmol) were dissolved in DMF (2 ml) and stirred under nitrogen for 30 mins. 6-(1H-Indol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine (100 mg, 0.30 mmol) was added and the reaction was stirred for 5 h. Further (3-methyl-1H-pyrazol-1-yl)acetic acid (38 mg, 0.27 mmol), HATU (126 mg, 0.33 mmol) and DIPEA (0.158 ml, 0.91 mmol) in DMF (1 ml) was added, after stirring together for 10 mins, and the reaction was stirred for 2 days under a nitrogen atmosphere at RT. The reaction was loaded on to a PS-aminopropyl cartridge (10 g) and eluted with DCM. Appropriate fractions were combined and evaporated in vacuo. MeOH (2 ml) and 2 M HCl (aq) (45 μl, 0.09 mmol) were added and stirred for ˜30 mins at RT. The solvent was evaporated in vacuo and the residue was dissolved in MeOH:DMSO (2 ml; 1:1, v/v) and purified by Mass Directed Automated Preparative HPLC using method B. The solvent was dried under a stream of nitrogen to give title compound (31 mg).

Workup

  1. stirringthe reaction was stirred for 5 h
  2. stirringafter stirring together for 10 mins
  3. stirringthe reaction was stirred for 2 days under a nitrogen atmosphere at RT
  4. washeluted with DCM
  5. customevaporated in vacuo
  6. stirringstirred for ˜30 mins at RT
  7. customThe solvent was evaporated in vacuo
  8. dissolutionthe residue was dissolved in MeOH
  9. custom1:1, v/v) and purified by Mass Directed Automated Preparative HPLC
  10. customThe solvent was dried under a stream of nitrogen

Sources & evidence

ORD record
ord-fea9886022444b66988b7cbe83542210
Source dataset
uspto-grants-2013_09
Patent number
US08536169B2

Reaction notes

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