Diisopropylethylamine → 6-(1-Methyl-1H-pyrazol-4-yl)-3-(1H-pyrrolo[2,3-b]pyridine-3-ylmethyl)-[1,2,4]triazolo[4,3-b]pyridazine

HRID 655278Notes

Reaction equation

HRID 655278 reaction equation
[NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]([CH2:10][C:11](O)=O)=[CH:2]1.[CH3:14][N:15]1[CH:19]=[C:18]([C:20]2[N:25]=[N:24][C:23]([NH:26][NH2:27])=[CH:22][CH:21]=2)[CH:17]=[N:16]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH3:14][N:15]1[CH:19]=[C:18]([C:20]2[CH:21]=[CH:22][C:23]3[N:24]([C:11]([CH2:10][C:3]4[C:4]5[C:5](=[N:6][CH:7]=[CH:8][CH:9]=5)[NH:1][CH:2]=4)=[N:27][N:26]=3)[N:25]=2)[CH:17]=[N:16]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 250673241H-pyrrolo(2,3-b)pyridine-3-acetic acidHCID 580751723-Hydrazinyl-6-(1-methyl-1H-pyrazol-4-yl)pyridazine

Product 1

HCID 593202626-(1-Methyl-1H-pyrazol-4-yl)-3-(1H-pyrrolo[2,3-b]pyridine-3-ylmethyl)-[1,2,4]triazolo[4,3-b]pyridazineYield 3.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 20 ml vial 52 mgs (0.295 mmol) of (1H-pyrrolo[2,3-b]pyridine-3-yl)-acetic acid, 1.2 eq. (0.354 mmol) of 0-(7-azabenzotriazole-1-yl)-N,N,N,N′-tetramethyluroniumhexafluoro-phosphate, 1.5 eq. (0.443 mmol) [6-(1-methyl-1H-pyrazol-4-yl)-pyridazin-3-yl]-hydrazine and 4 eq. (1.18 mmol) N,N-diisopropylethylamine were added and dissolved in 4 mls of dimethyl-formamide. The reaction mixture was stirred at room temperature for 18 h. After such time the dimethylformamide was removed in vacuo and acetic acid (4 mls) was added to the residue and heated to 60° C. for 4 hours. The solvent was removed in vacuo purification via preparative HPLC eluting with dichloromethane:methanol 95:5 returned the title compound (3 mgs, 3% yield) as an off white solid. Analytical data presented in Table 1.

Workup

  1. customAfter such time the dimethylformamide was removed in vacuo and acetic acid (4 mls)
  2. additionwas added to the residue
  3. temperatureheated to 60° C. for 4 hours
  4. customThe solvent was removed in vacuo purification via preparative HPLC
  5. washeluting with dichloromethane:methanol 95:5

Sources & evidence

ORD record
ord-a8c704997509456d9f29daa3128ea80e
Source dataset
uspto-grants-2011_12
Patent number
US08071581B2

Reaction notes

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