HCID 11518123, compound → HCID 58335761, compound

HRID 1890695Notes

Reaction equation

HRID 1890695 reaction equation
[CH3:1][C:2]1([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([Sn](CCCC)(CCCC)CCCC)[N:8]=2)[O:6][CH2:5][CH2:4][O:3]1.Br[C:27]1[N:31]2[N:32]=[C:33]([N:36]3[CH2:40][CH2:39][CH2:38][CH:37]3[C:41]3[CH:46]=[C:45]([F:47])[CH:44]=[CH:43][C:42]=3F)[CH:34]=[CH:35][C:30]2=[N:29][CH:28]=1>C1(C)C=CC=CC=1>[F:47][C:45]1[CH:46]=[C:41]([C@H:37]2[CH2:38][CH2:39][CH2:40][N:36]2[C:33]2[CH:34]=[CH:35][C:30]3[N:31]([C:27]([C:9]4[CH:10]=[CH:11][CH:12]=[C:7]([C:2]5([CH3:1])[O:3][CH2:4][CH2:5][O:6]5)[N:8]=4)=[CH:28][N:29]=3)[N:32]=2)[CH:42]=[CH:43][CH:44]=1

Participants

4

Reactant 2

HCID 11518123HCID 11518123, compoundHCID 583354643-Bromo-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine

Product 1

HCID 58335761HCID 58335761, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
110 °C

Procedure

In step 15-1, 2-(2-methyl-1,3-dioxolan-2-yl)-6-(tributylstannyl)pyridine (57 g, 124 mmol) in 100 mL of toluene was cannula transferred under the argon atmosphere to a suspension of 3-bromo-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (15-1) (30 g, 83 mmol) and tetrakis(triphenylphospine)palladium (4.8 mg, 4.15 mmol) in 500 mL of toluene. The resulting reaction mixture was heated to 110° C. for overnight. The reaction progress was monitored by LC/Mass. After the reaction was complete, the reaction vessel was cooled to room temperature and the solvent reduced to ⅓ of the original volume. The purification was performed by flash chromatography using pure ethyl acetate to afford (R)-6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(6-(2-methyl-1,3-dioxolan-2-yl)pyridine-2-yl)imidazo[1,2-b]pyridazine (15-2). 1H NMR (400 MHz, DMSO-d6) δ 8.10 (s, 1H), 8.09 (s br, 1H), 7.93 (d, 1H, J=9.6 Hz), 7.72 (m, 1H), 7.39 (m, 2H), 7.18 (m, 2H), 7.04 (m, 1H), 6.89 (br s, 1H), 5.16 (d, 1H, J=8.0 Hz), 4.02 (m, 3H), 3.91 (m, 2H), 3.68 (m, 2H), 2.48 (m, 1H), 2.05 (m, 2H), 1.88 (m, 1H), 1.69 (s, 3H). LCMS: m/z 446.2 (M+1).

Workup

  1. customThe resulting reaction mixture
  2. temperaturethe reaction vessel was cooled to room temperature
  3. customThe purification

Sources & evidence

ORD record
ord-ba7d4352e87e4534be3ec7ad49100025
Source dataset
uspto-grants-2013_08
Patent number
US08507488B2

Reaction notes

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