Acetonitrile → HCID 58588417, compound

HRID 1361709Notes

Reaction equation

HRID 1361709 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:18]=[C:19]([O:21][C:22]2[C:27]([C:28]3[CH:33]=[CH:32][N:31]=[C:30]([NH:34][CH3:35])[N:29]=3)=[CH:26][CH:25]=[CH:24][N:23]=2)[CH:20]=1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=1)=[O:6].[C:36](#N)[CH3:37].C[Si](C#C)(C)C>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.[Cu]I.CCN(CC)CC>[C:36]([C:2]1[CH:3]=[C:4]([CH:18]=[C:19]([O:21][C:22]2[C:27]([C:28]3[CH:33]=[CH:32][N:31]=[C:30]([NH:34][CH3:35])[N:29]=3)=[CH:26][CH:25]=[CH:24][N:23]=2)[CH:20]=1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:16])([F:15])[F:17])[CH:9]=1)=[O:6])#[CH:37]

Participants

7

Reactant 3

HCID 6342AcetonitrileHCID 66111TrimethylsilylacetyleneHCID 66970612HCID 66970612, compound

Product 1

HCID 58588417HCID 58588417, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 3-Bromo-5-[3-(2-methylamino-pyrimidin-4-yl)-pyridin-2-yloxy]-N-(3-trifluoromethyl-phenyl)-benzamide (110 mg, 0.20 mmol), acetonitrile (5 mL) and Et3N (1 mL) in a sealed tube was added trimethylsilyl acetylene (0.14 mL, 1.0 mmol) followed by PdCl2(PPh3)2 (14 mg, 0.02 mmol) and CuI (4.0 mg, 0.02 mmol). The tube was sealed and heated at 85° C. for 15 h. The mixture was allowed to cool to room temperature and concentrated under reduced pressure. The resulting crude mixture was reconstituted in methanol (5 mL), saturated with solid K2CO3 (˜200 mg) and allowed to stir at room temperature for 1 h. The resulting mixture was concentrated under reduced pressure and reconstituted in EtOAc (20 mL). The organic phase was washed successively with water (2×5 mL) and brine (1×5 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude was purified via RP-HPLC to afford the title compound as an off-white solid. MS m/z=490 [M+1]+, Calc'd for C26H18F3N5O2: 489.45.

Workup

  1. customThe tube was sealed
  2. temperatureto cool to room temperature
  3. concentrationconcentrated under reduced pressure
  4. concentrationThe resulting mixture was concentrated under reduced pressure
  5. washThe organic phase was washed successively with water (2×5 mL) and brine (1×5 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude was purified via RP-HPLC

Sources & evidence

ORD record
ord-30ec4031aee1414faf07fdcbe6b4c14b
Source dataset
uspto-grants-2011_02
Patent number
US07880000B2

Reaction notes

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