1,2-Dimethoxyethane → 8-(1-Ethyl-propyl)-2,6-dimethyl-3-(1-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-imidazo[1,2-b]pyridazine

HRID 226036Notes

Reaction equation

HRID 226036 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:23]2=[N:24][CH:25]=[CH:26][CH:27]=[C:22]2[CH:21]=[C:20]1B1OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO.O>[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([C:13]([C:20]3[N:19]([CH3:18])[C:23]4=[N:24][CH:25]=[CH:26][CH:27]=[C:22]4[CH:21]=3)=[C:14]([CH3:16])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2]

Participants

9

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 577526818-(1-Ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 688578811-Methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-pyrrolo[2,3-B]pyridine

Product 1

HCID 577526918-(1-Ethyl-propyl)-2,6-dimethyl-3-(1-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-imidazo[1,2-b]pyridazineYield 48%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine, 1-methyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (0.23 g, 0.89 mmol), 2M Na2CO3 (0.72 mL, 1.45 mmol), and 7:3:2 DME:Water: EtOH (5 mL) is degassed with nitrogen for 15 minutes. Pd(PPh3)4 (0.051 g, 0.044 mmol) is added and the solution is heated at a reflux for three 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 (15%-30% EtOAc gradient) to furnish the title compound (0.12 g, 0.35 mmol, 48%). 1H NMR (CDCl3), δ 0.90 (t, J=7.5 Hz, 6H), 1.78-1.95 (m, 4H), 2.50 (s, 3H), 2.53 (s, 3H), 3.32-3.40 (m, 1H), 3.74 (s, 3H), 6.64 (s, 1H), 6.72 (s, 1H), 7.11 (dd, J=8.3, 4.8 Hz, 1H), 7.96 (dd, J=8.3, 1.3 Hz, 1H), 8.40 (dd, J=4.8, 1.3 Hz, 1H) ppm. LC/MS (m/z): calcd. for C21H25N5 (M+H)+: 348.3. found: 348.2.

Workup

  1. temperaturethe solution is heated at
  2. temperaturea reflux for three 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 (15%-30% EtOAc gradient)

Sources & evidence

ORD record
ord-6a48f6b7eb224ce3bdeaee77467ef41c
Source dataset
uspto-grants-2009_07
Patent number
US07557103B2

Reaction notes

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