Triethylamine → HCID 66558445, compound

HRID 331169Notes

Reaction equation

HRID 331169 reaction equation
I[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=1.[F:10][C:11]1([F:35])[C:17]([CH3:19])([CH3:18])[O:16][CH2:15][C:14]([NH2:20])=[N:13][C@@:12]1([C:22]1[CH:27]=[C:26]([C:28]#[C:29][Si](C)(C)C)[CH:25]=[CH:24][C:23]=1[F:34])[CH3:21].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[NH2:20][C:14]1[CH2:15][O:16][C:17]([CH3:19])([CH3:18])[C:11]([F:35])([F:10])[C@:12]([C:22]2[CH:27]=[C:26]([C:28]#[C:29][C:2]3[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=3)[CH:25]=[CH:24][C:23]=2[F:34])([CH3:21])[N:13]=1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 2724141Tetrabutylammonium FluorideHCID 157659656-Iodopyridine-3-carbonitrileHCID 68380191HCID 68380191, compound

Product 1

HCID 66558445HCID 66558445, compoundYield 40%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 67553Tetrabutylammonium IodideCatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent4×

Conditions

Temperature
40 °C

Procedure

A dried flask was charged under an atmosphere of argon with a solution of 6-iodo-nicotinonitrile (25 mg, 109 μmol) and (R)-6,6-Difluoro-5-(2-fluoro-5-trimethylsilanylethynyl-phenyl)-5,7,7-trimethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-ylamine (50 mg, 131 μmol) in dimethylformamide (368 μl) (solution A). A second dried flask was charged under an atmosphere of argon with dimethylformamide (368 μl), then successively with bis(triphenylphosphine)palladium(II)chloride (5.47 mg, 7.6 μmol), triphenylphoshine (1.14 mg, 4.4 μmol), copper(I)iodide (0.42 mg, 2.1 μmol), triethylamine (55.2 mg, 0.545 mmol), and tetrabutylammoniumiodide (41.1 mg, 109 μmol) were added. The mixture was heated to 40° C., and solution A was added dropwise. The temperature was raised to 60° C. and a solution of tetrabutylammoniumfluoride (1M in tetrahydrofuran; 142 μl) was added dropwise. Stirring was continued for 16 hours. For the workup, the reaction mixture was evaporated at reduced pressure and the residue directly purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 50:50 as the eluent. The 6-[3-((R)-3-amino-6,6-difluoro-5,7,7-trimethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-5-yl)-4-fluoro-phenylethynyl]-nicotinonitrile (18 mg, 40% yield) was obtained as a colorless oil. MS (ISP): m/z=413.2 [M+H]+.

Workup

  1. temperatureThe temperature was raised to 60° C.
  2. customFor the workup, the reaction mixture was evaporated at reduced pressure
  3. customthe residue directly purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 50:50 as the eluent

Sources & evidence

ORD record
ord-b14b3b22bfa54d2988802c1293cd8340
Source dataset
uspto-grants-2014_11
Patent number
US08877744B2

Reaction notes

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