Triethylamine → HCID 66558445、化合物

HRID 331169ノート

反応式

HRID 331169 の反応式
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

参加物

10

反応物 5

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 2724141Tetrabutylammonium FluorideHCID 157659656-Iodopyridine-3-carbonitrileHCID 68380191HCID 68380191、化合物

生成物 1

HCID 66558445HCID 66558445、化合物収率 40%

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 67553Tetrabutylammonium Iodide触媒HCID 6102075Dichlorobis(triphenylphosphine)palladium触媒HCID 6228Dimethylformamide溶媒4 回

反応条件

温度
40 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-b14b3b22bfa54d2988802c1293cd8340
出典データセット
uspto-grants-2014_11
特許番号
US08877744B2

反応ノート

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