Sodium Carbonate → N-(6-(5-amino-6-chloropyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide

HRID 1162471Notes

Reaction equation

HRID 1162471 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12](=[O:14])[CH3:13])[N:10]=2)[N:7]=1.[Cl:15][C:16]1[C:21]([NH2:22])=[CH:20][C:19](C2OC(C)(C)C(C)(C)O2)=[CH:18][N:17]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1.O>[NH2:22][C:21]1[CH:20]=[C:19]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([CH:8]=[C:9]([NH:11][C:12](=[O:14])[CH3:13])[N:10]=3)[N:7]=2)[CH:18]=[N:17][C:16]=1[Cl:15]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 59519510N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamideHCID 866319652-Chloro-5-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)pyridin-3-amine

Product 1

HCID 57749424N-(6-(5-amino-6-chloropyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamideYield 49.6%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamide (0.05 g, 0.2 mmol, Aurigene, Bangalore, India), 2-chloro-5-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)pyridin-3-amine from Step 1 (0.07 g, 0.3 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (0.01 g, 0.02 mmol), sodium carbonate (0.05 g, 0.5 mmol), and dioxane-H2O (4:1, 2 mL). Ar was bubbled in for 1 minute. The reaction mixture was sealed and heated at 100° C. for 2 h before cooled down to room temperature. The mixture was filtered through a Celite® (diatomaceous earth) pad, the filtercake was washed with MeOH-DCM (50%), and the filtrate was concentrated in vacuo. Purification by silica gel chromatography (10 to 50% MeOH/CH2Cl2) provided N-(6-(5-amino-6-chloropyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (0.03 g, 42% yield) as a white solid. MS (ESI positive ion) m/z: 303 (M+1). 1H NMR (400 MHz, DMSO-d6): δ ppm 2.11 (s, 3H), 5.84 (s, 2H), 7.72 (d, J=9.39 Hz, 1H), 7.77 (d, J=2.15 Hz, 1H), 8.08 (d, J=9.39 Hz, 1H), 8.23 (d, J=2.15 Hz, 1H), 8.28 (s, 1H), 10.93 (s, 1H).

Workup

  1. customA glass microwave reaction vessel
  2. customAr was bubbled in for 1 minute
  3. customThe reaction mixture was sealed
  4. temperaturebefore cooled down to room temperature
  5. filtrationThe mixture was filtered through a Celite® (diatomaceous earth) pad
  6. washthe filtercake was washed with MeOH-DCM (50%)
  7. concentrationthe filtrate was concentrated in vacuo
  8. customPurification by silica gel chromatography (10 to 50% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-d2f79298242b4ef995bac2564e711d34
Source dataset
uspto-grants-2010_10
Patent number
US07820665B2

Reaction notes

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