Triethylamine → HCID 66558445, 화합물

HRID 331169노트

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HRID 331169 반응식
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

참가 물질

10

반응물 5

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

생성물 1

HCID 66558445HCID 66558445, 화합물수율 40%

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 67553Tetrabutylammonium Iodide촉매HCID 6102075Dichlorobis(triphenylphosphine)palladium촉매HCID 6228Dimethylformamide용매4회

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온도
40 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-b14b3b22bfa54d2988802c1293cd8340
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877744B2

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