Sodium Carbonate → 3-(1,5-dimethyl-1H-indol-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 226038Notes

Reaction equation

HRID 226038 reaction equation
[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([C:13](I)=[C:14]([CH3:16])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2].[CH3:18][N:19]1[C:27]2[C:22](=[CH:23][C:24]([CH3:28])=[CH:25][CH:26]=2)[CH:21]=[C:20]1B(O)O.C([O-])([O-])=O.[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2].C(O)CC>[CH3:18][N:19]1[C:27]2[C:22](=[CH:23][C:24]([CH3:28])=[CH:25][CH:26]=2)[CH:21]=[C:20]1[C:13]1[N:8]2[N:9]=[C:10]([CH3:12])[CH:11]=[C:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[C:7]2=[N:15][C:14]=1[CH3:16]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 577526818-(1-Ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 585062151,5-dimethyl-1H-indole-2-boronic acid

Product 1

HCID 577526543-(1,5-dimethyl-1H-indol-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineYield 10%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 10311-PropanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.10 g, 0.29 mmol), 1,5-dimethyl-1H-indole-2-boronic acid (0.060 g, 0.32 mmol), 2M Na2CO3 (0.22 mL, 0.44 mmol), and n-PrOH (1.5 mL) is degassed with nitrogen for 10 minutes. Pd(OAc)2 (0.0013 g, 0.0058 mmol), and PPh3 (0.0046 g, 0.017 mmol) are added and the solution is heated at a reflux for two days. The solution is diluted with CH2Cl2 (50 mL), washed with 10% Na2CO3 (30 mL), water (30 mL), brine (30 mL), dried over MgSO4, filtered and concentrated. The material is purified by ISCO (30%-50% EtOAc gradient) to furnish the title compound (0.010 g, 0.028 mmol, 10%). 1H NMR (CDCl3), δ 0.90 (t, J=7.5 Hz, 6H), 1.75-1.95 (m, 4H), 2.48 (s, 3H), 2.49 (s, 3H), 2.51 (s, 3H), 3.32-3.41 (m, 1H), 3.58 (s, 3H), 6.59 (s, 1H), 6.70 (s, 1H), 7.12 (dd, J=8.4, 1.8 Hz, 1H), 7.31 (d, J=8.4 Hz, 1H), 7.47 (s, 1H) ppm. LC/MS (m/z): calcd. for C23H28N4 (M+H)+: 361.6; found: 361.2.

Workup

  1. temperaturethe solution is heated at
  2. temperaturea reflux for two days
  3. washwashed with 10% Na2CO3 (30 mL), water (30 mL), brine (30 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe material is purified by ISCO (30%-50% EtOAc gradient)

Sources & evidence

ORD record
ord-257c4afdacd04fb8bea31d7334116608
Source dataset
uspto-grants-2009_07
Patent number
US07557103B2

Reaction notes

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