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 246550노트

반응식

HRID 246550 반응식
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]

참가 물질

9

반응물 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

생성물 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-carboxamide수율 32.3%

시약·촉매·용매 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 3283Diethyl Ether용매HCID 8857Ethyl Acetate용매

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온도
90 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-671117fb22c844d2b24c226f149ef6c9
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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