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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
ノート
印刷プレビュー

反応式

HRID 1398563 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 8028
Tetrahydrofuran
溶媒
3 回

実験手順

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)+

後処理

  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)

出典と根拠

ORDレコード
ord-16a139b0e0c54bcfba963729fc2e89b1
出典データセット
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08901313B2

反応ノート

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