Sodium Carbonate → HCID 54671277, compound

HRID 407980Notes

Reaction equation

HRID 407980 reaction equation
[F:1][C:2]1[CH:35]=[C:34]([S:36]([CH3:39])(=[O:38])=[O:37])[C:33]([F:40])=[CH:32][C:3]=1[O:4][C@H:5]1[CH2:9][CH2:8][N:7]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]3[N:21]=[CH:20][C:19](B4OC(C)(C)C(C)(C)O4)=[CH:18][N:17]=3)[CH2:12][CH2:11]2)[C:6]1=[O:31].Cl[C:42]1[N:47]=[CH:46][CH:45]=[CH:44][N:43]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[N:43]1[CH:44]=[CH:45][CH:46]=[N:47][C:42]=1[C:19]1[CH:18]=[N:17][C:16]([N:13]2[CH2:14][CH2:15][CH:10]([N:7]3[CH2:8][CH2:9][C@H:5]([O:4][C:3]4[CH:32]=[C:33]([F:40])[C:34]([S:36]([CH3:39])(=[O:38])=[O:37])=[CH:35][C:2]=4[F:1])[C:6]3=[O:31])[CH2:11][CH2:12]2)=[N:21][CH:20]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 744042-ChloropyrimidineHCID 67469795HCID 67469795, compound

Product 1

HCID 54671277HCID 54671277, compoundYield 47.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

(S)-3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-1-(1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one (173 mg, 0.299 mmol), 2-chloropyrimidine (41.1 mg, 0.359 mmol) and 2M Na2CO3 (748 μL, 1.50 mmol) were dissolved in dioxane (3 mL) and purged with nitrogen. Pd(PPh3)4 (34.6 mg, 0.0299 mmol) was added and the reaction was heated to 80° C. for 3 hours. The reaction was cooled to ambient temperature, partitioned between water and CH2Cl2, extracted twice, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (eluting with 90 to 100% EtOAc in hexanes) to afford (S)-1-(1-(2,5′-bipyrimidin-2′-yl)piperidin-4-yl)-3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)pyrrolidin-2-one (76 mg, 0.143 mmol, 47.9% yield) as a white solid. Mass spectrum (apci) m/z=531.2 (M+H).

Workup

  1. custompurged with nitrogen
  2. temperatureThe reaction was cooled to ambient temperature
  3. custompartitioned between water and CH2Cl2
  4. extractionextracted twice
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified over silica gel (eluting with 90 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-49700955e29947a8b232dff35d73e344
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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