Sodium Carbonate → HCID 10160106, compound

HRID 2184013Notes

Reaction equation

HRID 2184013 reaction equation
Br[C:2]1[N:6]2[CH:7]=[CH:8][C:9]([C:11]([F:14])([F:13])[F:12])=[N:10][C:5]2=[N:4][CH:3]=1.[F:15][C:16]1[CH:21]=[CH:20][C:19](B2OC(C)(C)C(C)(C)O2)=[CH:18][C:17]=1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[S:37]([CH3:40])(=[O:39])=[O:38].C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.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:15][C:16]1[CH:21]=[CH:20][C:19]([C:2]2[N:6]3[CH:7]=[CH:8][C:9]([C:11]([F:14])([F:13])[F:12])=[N:10][C:5]3=[N:4][CH:3]=2)=[CH:18][C:17]=1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[S:37]([CH3:40])(=[O:39])=[O:38]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 113914623-Bromo-7-(trifluoromethyl)imidazo[1,2-a]pyrimidineHCID 222853232-(2-Fluoro-2'-(methanesulfonyl)biphenyl-5-yl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane

Product 1

HCID 10160106HCID 10160106, compoundYield 79.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A stirred mixture of 3-bromo-7-trifluoromethylimidazo[1,2-α]pyrimidine (0.1073 g, 0.403 mmol) and 2-(2-fluoro-2′-(methanesulfonyl)biphenyl-5-yl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (228 mg, 0.607 mmol) in tetrahydrofuran (5 ml) and 2M aqueous sodium carbonate (containing 1 ml/l of 40 wt % tetrabutylammonium hydroxide in water) (0.605 ml, 1.21 mmol) was degassed by bubbling nitrogen through the mixture for 15 min. Tetrakis(triphenylphosphine)palladium(0) (24.6 mg, 0.0213 mmol) was then added and the mixture was heated at 65° C. under nitrogen for 6 h. After cooling, the mixture was partitioned between ethyl acetate (25 ml) and water (15 ml). The aqueous layer was extracted further with ethyl acetate (2×25 ml) and the combined organic extracts were dried over anhydrous sodium sulphate and evaporated in vacuo. The residue was purified by flash chromatography on silica gel, eluting with isohexane on a gradient of ethyl acetate (40-50%), to afford 3-[2-fluoro-2′-(methanesulfonyl)biphenyl-5-yl]-7-trifluoromethylimidazo[1,2-α]pyrimidine as a yellow solid (139 mg, 79%): mp 211-213° C. (ethyl acetate/isohexane); δH (360 MHz, CDCl3) 2.89 (3H, s), 7.27 (1H, d, J 6.9), 7.40 (1H, td, J 1.2, 9.0), 7.46 (1H, dd, J 1.2, 7.4), 7.62-7.66 (2H, m), 7.68 (1H, td, J 1.6, 7.4), 7.74 (1H, td, J 1.6, 7.4), 8.10 (1H, s), 8.29 (1H, dd, J 1.4, 8.0), 9.22 (1H, d, J 7.0); MS (ES+) m/z 436 [M+H]+. Anal. Found: C, 55.02; H, 3.02; N, 9.23%. Required for C20H13F4N3O2S.0.1H2O: C, 54.94; H, 3.04; N, 9.61%.

Workup

  1. customwas degassed
  2. customby bubbling nitrogen through the mixture for 15 min
  3. temperatureAfter cooling
  4. customthe mixture was partitioned between ethyl acetate (25 ml) and water (15 ml)
  5. extractionThe aqueous layer was extracted further with ethyl acetate (2×25 ml)
  6. dry with materialthe combined organic extracts were dried over anhydrous sodium sulphate
  7. customevaporated in vacuo
  8. customThe residue was purified by flash chromatography on silica gel
  9. washeluting with isohexane on a gradient of ethyl acetate (40-50%)

Sources & evidence

ORD record
ord-48a58611f86543168b7cdfa580cc9122
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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