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Lithium diisopropylamide → 4-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)but-3-yn-2-ol

HRID 1398563
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HRID 1398563 반응식
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[CH:18])[CH:15]=3)[C:10]([C:19](N(C)C)=O)=[N:9]2)[CH:5]=[CH:4][N:3]=1.[Li+].CC([N-]C(C)C)C.[CH3:32][Si:33]([CH3:47])([CH3:46])[CH2:34][CH2:35][O:36][CH2:37][N:38]1[CH:42]=[CH:41][N:40]=[C:39]1[C:43](=[O:45])[CH3:44]>C1COCC1>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[C:18][C:43]([C:39]4[N:38]([CH2:37][O:36][CH2:35][CH2:34][Si:33]([CH3:32])([CH3:47])[CH3:46])[CH:42]=[CH:41][N:40]=4)([OH:45])[CH3:44])[CH:15]=3)[C:10]([CH3:19])=[N:9]2)[CH:5]=[CH:4][N:3]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 2724682Lithium diisopropylamideHCID 598646231-(1-{[2-(Trimethylsilyl)ethoxy]methyl}imidazol-2-yl)ethanoneHCID 866695911-(2-aminopyrimidin-4-yl)-6-ethynyl-N,N-dimethylindazole-3-carboxamide

생성물 1

HCID 681816514-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)but-3-yn-2-ol

시약·촉매·용매 1

HCID 8028
Tetrahydrofuran
용매
3회

실험 절차

To a solution of 1-(2-aminopyrimidin-4-yl)-6-ethynyl-N,N-dimethylindazole-3-carboxamide (200 mg, 0.8 mmol) in THF (2 mL) at −78° C. under nitrogen was added 2M LDA in THF (1.40 mL, 2.81 mmol). After 1 hour, 1-(1-{[2-(trimethylsilyl)ethoxy]methyl}imidazol-2-yl)ethanone (771.45 mg, 3.21 mmol) in THF (1.0 mL) was added. After stirring for 15 minutes, the reaction mixture was allowed to warm to RT and stirred for 2 hr. The reaction mixture was quenched by addition of saturated aqueous ammonium chloride (3 mL) and the volatiles were removed in vacuo. The reaction mixture was diluted with DCM (10 ml) and washed with water (2 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography (Biotage, 1-12% methanol gradient in DCM) to surrender the title compound as a yellow solid: 1H NMR (500 MHz, DMSO) delta −0.19 (9H, s), 0.83-0.77 (2H, m), 2.01 (3H, s), 2.57 (3H, s), 3.59-3.49 (2H, m), 5.62 (1H, d, J=10.3 Hz), 5.78 (1H, d, J=10.2 Hz), 6.42 (1H, s), 6.86 (1H, d, J=1.1 Hz), 6.96 (2H, s), 7.03 (1 H, d, J=5.5 Hz), 7.27 (1H, d, J=1.0 Hz), 7.36 (1H, dd, J=8.1, 1.1 Hz), 7.84 (1H, d, J=8.2 Hz), 8.25 (1H, d, J=5.5 Hz), 8.85 (1H, s); LC-MS: m/z=+490.10 (M+H)+

후처리

  1. stirringstirred for 2 hr
  2. customThe reaction mixture was quenched by addition of saturated aqueous ammonium chloride (3 mL)
  3. customthe volatiles were removed in vacuo
  4. additionThe reaction mixture was diluted with DCM (10 ml)
  5. washwashed with water (2 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography (Biotage, 1-12% methanol gradient in DCM)

출처 및 근거

ORD 기록
ord-16a139b0e0c54bcfba963729fc2e89b1
출처 데이터셋
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08901313B2

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