Triethylamine → 6-(2-(2,5-Difluorophenyl)pyrrolidin-1-yl)-3-(6-fluoropyridin-2-yl)imidazo[1,2-b]pyridazine

HRID 1890679Notes

Reaction equation

C(N(CC)CC)C.[F:8][C:9]1[N:14]=[C:13]([Sn](CCCC)(CCCC)CCCC)[CH:12]=[CH:11][CH:10]=1.Br[C:29]1[N:33]2[N:34]=[C:35]([N:38]3[CH2:42][CH2:41][CH2:40][CH:39]3[C:43]3[CH:48]=[C:47]([F:49])[CH:46]=[CH:45][C:44]=3[F:50])[CH:36]=[CH:37][C:32]2=[N:31][CH:30]=1>C1(C)C=CC=CC=1>[F:50][C:44]1[CH:45]=[CH:46][C:47]([F:49])=[CH:48][C:43]=1[CH:39]1[CH2:40][CH2:41][CH2:42][N:38]1[C:35]1[CH:36]=[CH:37][C:32]2[N:33]([C:29]([C:13]3[CH:12]=[CH:11][CH:10]=[C:9]([F:8])[N:14]=3)=[CH:30][N:31]=2)[N:34]=1

Participants

Conditions

Temperature: 100 °C

Procedure

In step 5-1, triethylamine (0.045 mL, 0.29 mmol), tetrakis(triphenylphospine)palladium (0) (12 mg, 0.01 mmol), and 6-fluoro-2(tributylstannyl)pyridine (80 mg, 0.201 mmol) were added to a solution of 3-bromo-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (6-6) (53 mg, 0.13 mmol) in 3 mL of toluene. The reaction mixture was heated to 100° C. and stirred for 6 hours at 100° C. The reaction mixture was then cooled to room temperature and purified using flash chromatography (ethyl acetate and hexanes (1:1)) giving 6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-(6-fluoropyridin-2-yl)imidazo[1,2-b]pyridazine (5-1). 1H NMR (400 MHz, D3 acetonitrile) δ ppm 8.35-8.17 (m, 2H), 8.02-7.83 (m, 1H), 7.48-7.22 (m, 3H), 7.15-6.92 (m, 3H), 5.42 (br d, J=5.8 Hz, 1H), 4.12-3.99 (m, 1H), 3.81-3.72 (m, 1H), 2.70-2.56 (m, 1H), 2.30-2.06 (m, 3H). LCMS observed m/z 396.1

Workup

temperatureThe reaction mixture was then cooled to room temperature
custompurified

Sources & evidence

ORD record: ord-ae0499fd10624227ba6cbee2c3eddcf2
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507488B2

Reaction notes

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