2-(Methylthio)-4-(tributylstannyl)pyrimidine → (S)-2-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-5-(2-(methylthio)pyrimidin-4-yl)pyridazin-3(2H)-one

HRID 2365827Notes

Reaction equation

HRID 2365827 reaction equation
[Si]([O:8][CH2:9][C@@H:10]([N:19]1[C:24](=[O:25])[CH:23]=[C:22](I)[CH:21]=[N:20]1)[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([F:18])[CH:12]=1)(C(C)(C)C)(C)C.[CH3:27][S:28][C:29]1[N:34]=[C:33]([Sn](CCCC)(CCCC)CCCC)[CH:32]=[CH:31][N:30]=1>CN1C(=O)CCC1.C(OCC)(=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([C@H:10]([N:19]2[C:24](=[O:25])[CH:23]=[C:22]([C:31]3[CH:32]=[CH:33][N:34]=[C:29]([S:28][CH3:27])[N:30]=3)[CH:21]=[N:20]2)[CH2:9][OH:8])=[CH:12][C:13]=1[F:18]

Participants

7

Reactant 2

HCID 27632612-(Methylthio)-4-(tributylstannyl)pyrimidineHCID 86696678(S)-2-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-5-iodopyridazin-3(2H)-one

Product 1

HCID 86696679(S)-2-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-5-(2-(methylthio)pyrimidin-4-yl)pyridazin-3(2H)-oneYield 80.6%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of (S)-2-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-5-iodopyridazin-3(2H)-one (0.402 g, 0.790 mmol), 2-(methylthio)-4-(tributylstannyl)pyrimidine (0.361 g, 0.869 mmol), copper(I) iodide (0.0150 g, 0.0790 mmol) and PdCl2(PPh3)2 (0.0555 g, 0.0790 mmol) in NMP (4 mL) was heated to 120° C. under Ar for 16 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (200 mL). The organics were washed with brine (3×50 mL), dried, filtered and concentrated. The crude product was purified via column chromatography, eluting with hexanes/ethyl acetate (1:1) to give (S)-2-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-5-(2-(methylthio)pyrimidin-4-yl)pyridazin-3(2H)-one (0.25 g, 79%). m/z (APCI-pos) M+1=393.0, 395.0.

Workup

  1. washThe organics were washed with brine (3×50 mL)
  2. customdried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified via column chromatography
  6. washeluting with hexanes/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-28f6b88bcb4445d6877ef17131d9b9ba
Source dataset
uspto-grants-2014_04
Patent number
US08697715B2

Reaction notes

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