Dimethylformamide → N-tert-butyl-2-(6-fluoroimidazo[1,5-a]pyridin-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246550ノート

反応式

HRID 246550 の反応式
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:5]2=[N:6][CH:7]=1.[F:26][C:27]1[CH:28]=[CH:29][C:30]2[N:31]([CH:33]=[N:34][C:35]=2[Sn](CCCC)(CCCC)CCCC)[CH:32]=1.CN(C=O)C>CCOCC.C(OCC)(=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:35]3[N:34]=[CH:33][N:31]4[CH:32]=[C:27]([F:26])[CH:28]=[CH:29][C:30]=34)[N:3]=2)[N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

参加物

9

反応物 3

HCID 6228DimethylformamideHCID 712799216-Fluoro-1-tributylstannyl-imidazo[1,5-a]pyridineHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

生成物 1

HCID 71280199N-tert-butyl-2-(6-fluoroimidazo[1,5-a]pyridin-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide収率 32.3%

試薬・触媒・溶媒 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 3283Diethyl Ether溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

To a mixture of 2-bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (250 mg, 585 μmol), 6-fluoro-1-(tributylstannyl)imidazo[1,5-a]pyridine (400 mg, 564 μmol), tetrakis(triphenylphosphine)palladium (0) (33.8 mg, 29.2 μmol) and copper (I) iodide (22.3 mg, 117 μmol) was added DMF (5.85 mL) and the reaction mixture heated to 90° C. under N2. After 16 h the reaction was diluted with ether, ethyl acetate and water. The organic phase was separated and washed with water (1×) and brine (2×) then dried (MgSO4), filtered and concentrated in vacuo. Purification by chromatography (silica, 30-80% ethyl acetate/hexanes) gave N-tert-butyl-2-(6-fluoroimidazo[1,5-a]pyridin-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (88 mg, 182 μmol, 31.2%) as a yellow solid. MS (M+H)+=483.3; 1H NMR (CDCl3-d) δ: 9.34 (s, 1H), 8.54 (m, 1H), 8.34 (s, 2H), 8.04 (m, 1H), 7.98 (s, 1H), 6.9 (m, 1H), 5.74 (s, 2H), 3.61 (d, J=8.3 Hz, 2H), 1.66 (s, 9H); 0.98 (t, J=8.3 Hz, 2H), 0.0 (s, 9H).

後処理

  1. customThe organic phase was separated
  2. washwashed with water (1×) and brine (2×)
  3. dry with materialthen dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by chromatography (silica, 30-80% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-671117fb22c844d2b24c226f149ef6c9
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

読み込み中…