Cyclopropanecarbonyl chloride → HCID 59233190, compound

HRID 1925156Notes

Reaction equation

HRID 1925156 reaction equation
OC(C(F)(F)F)=O.[Br:8][C:9]1[CH:10]=[CH:11][C:12]2[N:13]([C:15]([CH:18]([C:20]3[CH:21]=[CH:22][C:23]4[N:24]([CH:26]=[C:27]([NH2:29])[N:28]=4)[N:25]=3)[CH3:19])=[N:16][N:17]=2)[CH:14]=1.CCN(C(C)C)C(C)C.[CH:39]1([C:42](Cl)=[O:43])[CH2:41][CH2:40]1>C(Cl)Cl>[Br:8][C:9]1[CH:10]=[CH:11][C:12]2[N:13]([C:15]([CH:18]([C:20]3[CH:21]=[CH:22][C:23]4[N:24]([CH:26]=[C:27]([NH:29][C:42]([CH:39]5[CH2:41][CH2:40]5)=[O:43])[N:28]=4)[N:25]=3)[CH3:19])=[N:16][N:17]=2)[CH:14]=1

Participants

5

Reactant 3

HCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 86639821HCID 86639821, compound

Product 1

HCID 59233190HCID 59233190, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-(1-(6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethyl)imidazo[1,2-b]pyridazin-2-amine TFA salt (250 mg, 0.52 mmol) in CH2Cl2 was added DIEA (0.65 g, 5.0 mmol) followed by cyclopropanecarbonyl chloride (0.16 g, 1.5 mmol). The reaction was stirred at ambient temperature for 30 min. Solvent was removed via rotary evaporation and the resulting residue was reconstituted in MeOH (10 mL). NH4OH (0.5 mL) was added and the reaction was stirred at ambient temperature for 1 hr. The reaction was then concentrated to dryness and the resulting material was dissolved in EtOAc, washed with saturated NaHCO3, dried with MgSO4, filtered and concentrated to dryness. The crude material was purified via MPLC (5% MeOH/0.1% NH4OH/EA) to provide the title compound, N-(6-(1-(6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethyl)imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide 48 (0.22 g, 0.52 mmol, 100%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.73-0.87 (m, 4 H) 1.83-1.99 (m, 4 H) 5.17 (d, J=7.07 Hz, 1 H) 7.38-7.57 (m, 3 H) 7.80 (d, J=9.60 Hz, 1 H) 7.99 (d, J=9.09 Hz, 1 H) 8.78 (s, 1 H) 11.14 (s, 1 H). ESI-MS:m/z 426.2 (M+H)+.

Workup

  1. customSolvent was removed via rotary evaporation
  2. additionNH4OH (0.5 mL) was added
  3. stirringthe reaction was stirred at ambient temperature for 1 hr
  4. concentrationThe reaction was then concentrated to dryness
  5. dissolutionthe resulting material was dissolved in EtOAc
  6. washwashed with saturated NaHCO3
  7. dry with materialdried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe crude material was purified via MPLC (5% MeOH/0.1% NH4OH/EA)

Sources & evidence

ORD record
ord-d7fd1e3783e34b23a88611611d6ec62b
Source dataset
uspto-grants-2012_05
Patent number
US08178534B2

Reaction notes

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