HCID 118554183, compound → HCID 76283448, compound

HRID 1480150Notes

Reaction equation

HRID 1480150 reaction equation
[CH3:1][S:2]([CH2:5][C:6]([NH:14][C:15]([C:17]1[CH:22]=[C:21]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])[C:20](Br)=[CH:19][N:18]=1)=[O:16])([CH3:13])[C:7]1[N:11]=[C:10]([CH3:12])[O:9][N:8]=1)(=[O:4])=[O:3].[Br-].[CH:31]1([Zn+])[CH2:33][CH2:32]1>C1COCC1>[CH3:1][S:2]([CH2:5][C:6]([NH:14][C:15]([C:17]1[CH:22]=[C:21]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])[C:20]([CH:31]2[CH2:33][CH2:32]2)=[CH:19][N:18]=1)=[O:16])([CH3:13])[C:7]1[N:11]=[C:10]([CH3:12])[O:9][N:8]=1)(=[O:4])=[O:3]

Participants

4

Reactant 2

HCID 118554183HCID 118554183, compoundHCID 178419765HCID 178419765, compound

Product 1

HCID 76283448HCID 76283448, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of 5-Bromo-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid [2-methanesulfonyl-1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide (Example 84c, 60 mg, 120 μmol) in dry THF (0.5 ml) under an argon atmosphere was added tetrakis(tripehylphosphine) palladium(0) (13.8 mg, 12.0 μmol) followed by cyclopropylzinc(II) bromide solution 0.5M in THF (527 μl, 263 μmol). The reaction mixture was then stirred at 100° C. under microwave radiation for 90 min. The reaction mixture was concentrated in vacuo. The residue was dissolved in ethylacetate and solution was extracted with an 1.0M aqueous solution of sodium bicarbonate. The organic phase was dried over sodium sulfate and evaporated down to dryness. The crude material was purified by preparative HPLC to yield the title compound (5.9 mg, 11%) as white solid. MS (ESI, m/z): 463.4 (M+H+).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in ethylacetate
  3. extractionsolution was extracted with an 1.0M aqueous solution of sodium bicarbonate
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. customevaporated down to dryness
  6. customThe crude material was purified by preparative HPLC

Sources & evidence

ORD record
ord-63213dec78de4a5196a08bb345aa6d6d
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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