2-(Methylthio)-4-(tributylstannyl)pyrimidine → HCID 58335875, compound

HRID 1890693Notes

Reaction equation

[CH3:1][S:2][C:3]1[N:8]=[C:7]([Sn](CCCC)(CCCC)CCCC)[CH:6]=[CH:5][N:4]=1.Br[C:23]1[N:28]=[C:27]([C:29]2[N:33]3[N:34]=[C:35]([N:38]4[CH2:42][CH2:41][CH2:40][C@@H:39]4[C:43]4[CH:48]=[CH:47][CH:46]=[C:45]([F:49])[CH:44]=4)[CH:36]=[CH:37][C:32]3=[N:31][CH:30]=2)[CH:26]=[CH:25][CH:24]=1>C1(C)C=CC=CC=1.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>[F:49][C:45]1[CH:44]=[C:43]([C@H:39]2[CH2:40][CH2:41][CH2:42][N:38]2[C:35]2[CH:36]=[CH:37][C:32]3[N:33]([C:29]([C:27]4[CH:26]=[CH:25][CH:24]=[C:23]([C:7]5[CH:6]=[CH:5][N:4]=[C:3]([S:2][CH3:1])[N:8]=5)[N:28]=4)=[CH:30][N:31]=3)[N:34]=2)[CH:48]=[CH:47][CH:46]=1

Participants

Conditions

Temperature: 110 °C

Procedure

In step 14-1, 2-(methylthio)-4-(tributylstannyl)pyrimidine (4.3 g, 13.2 mmol) and Pd(PPh3)4 (196 mg, 0.17 mmol) were added to a solution of (R)-3-(6-bromopyridin-2-yl)-6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (14-1) (1.5 g, 3.4 mmol) in toluene (35 mL). The mixture was degassed using N2 for 15 minutes and then heated at 110° C. for 2 hours. All the solvents were removed. The resulting mixture was purified by column chromatography (silica gel, EtOAc/CH3OH, 0 to 10% gradient) to give (R)-6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(6-(2-(methylthio)pyrimidin-4-yl)pyridin-2-yl)imidazo[1,2-b]pyridazine (14-2) as a light-yellow foam. LC/MS: 484.2 (MH+).

Workup

customThe mixture was degassed
customfor 15 minutes
customAll the solvents were removed
customThe resulting mixture was purified by column chromatography (silica gel, EtOAc/CH3OH, 0 to 10% gradient)

Sources & evidence

ORD record: ord-3964eb82c0644f1ba1db66e003258efc
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507488B2

Reaction notes

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