Sodium Hydroxide → HCID 11269675, compound

HRID 2356250Notes

Reaction equation

HRID 2356250 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH3:23])=[N:16][N:15]3[C:24]=2I)=[CH:8][CH:7]=1.[C:26]1(B(O)O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[OH-].[Na+]>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH3:23])=[N:16][N:15]3[C:24]=2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:8][CH:7]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 66827Phenylboronic AcidHCID 11374420HCID 11374420, compound

Product 1

HCID 11269675HCID 11269675, compound

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

2-[4-(2-Methoxyethoxy)phenyl]-3-iodo-6-propoxyimidazo[1,2-b]pyridazine (100 mg, 0.22 mmol) was dissolved with stirring in 1,2-dimethoxyethane (2.5 mL) under an atmosphere of nitrogen. Phenylboronic acid (30 mg, 0.24 mmol) was added followed by tetrakis(triphenylphosphine)-palladium(0) (20 mg). A solution of sodium hydroxide (18 mg, 0.44 mmol) in water (1 mL) was added. The resulting mixture was heated at 70° for 1 hour then cooled and partitioned between dichloromethane and water. The aqueous layer was extracted with dichloromethane and the combined organics dried and evaporated. The cream coloured solid residue was radially chromatographed on silica gel. Elution with 0-3% methanol in dichloromethane provided Compound 97 (74 mg) as a white solid. 1H n.m.r. (CDCl3) δ 1.00, t, J=7.3 Hz, 3H; 1.74-1.86, m, 2H; 3.45, s, 3H; 3.75, t, J=4.3 Hz, 2H; 4.13, t, J=4.3 Hz, 2H; 4.18, t, J=6.3 Hz, 2H; 6.70, d, J=9.5 Hz, 1H; 6.88, d, J=8.4 Hz, 2H; 7.35-7.47, m, 3H; 7.57, d, J=8.3 Hz 2H; 7.62, d, J=6.8 Hz, 2H; 7.82, d, J=9.3 Hz, 1H. Mass spectrum (APCI+) m/z 404 (M+H, 100%).

Workup

  1. temperatureThe resulting mixture was heated at 70° for 1 hour
  2. temperaturethen cooled
  3. custompartitioned between dichloromethane and water
  4. extractionThe aqueous layer was extracted with dichloromethane
  5. customthe combined organics dried
  6. customevaporated
  7. customwas radially chromatographed on silica gel
  8. washElution with 0-3% methanol in dichloromethane provided Compound 97 (74 mg) as a white solid

Sources & evidence

ORD record
ord-fbef5b2526314ee392ceacb2ae6cdec6
Source dataset
uspto-grants-2010_07
Patent number
US07759349B2

Reaction notes

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