tert-Butanol → (R)-1-[4-(4-Fluoro-1H-pyrrolo[2,3-b]pyridin-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]-propan-2-ol

HRID 1064234ノート

反応式

HRID 1064234 の反応式
[F:1][C:2]1[C:7]([O:8][C:9]2[C:14]3=[C:15]([CH3:19])[C:16]([OH:18])=[CH:17][N:13]3[N:12]=[CH:11][N:10]=2)=[CH:6][N:5]=[C:4]2[NH:20][CH:21]=[CH:22][C:3]=12.[CH3:23][C:24]([OH:27])(C)[CH3:25]>C(N(CC)CC)C>[F:1][C:2]1[C:7]([O:8][C:9]2[C:14]3=[C:15]([CH3:19])[C:16]([O:18][CH2:23][C@H:24]([OH:27])[CH3:25])=[CH:17][N:13]3[N:12]=[CH:11][N:10]=2)=[CH:6][N:5]=[C:4]2[NH:20][CH:21]=[CH:22][C:3]=12

参加物

4

反応物 2

HCID 6386tert-Butanol2 回HCID 98177604-(4-Fluoro-1H-pyrrolo[2,3-b]pyridin-5-yloxy)-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-6-ol

生成物 1

HCID 24884602(R)-1-[4-(4-Fluoro-1H-pyrrolo[2,3-b]pyridin-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]-propan-2-ol収率 56%

試薬・触媒・溶媒 1

HCID 8471Triethylamine溶媒

反応条件

温度
80 °C

実験手順

An oven dried sealed tube was charged with 4-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-ol (Example 5) (7.5 mg, 0.025 mmol), t-BuOH (0.25 mL), 0.5M of a solution of triethylamine in t-BuOH (5 μL, 0.0025 mmol) and R-(+)-propylene oxide (21 μL, 0.300 mmol). The tube was sealed and the mixture was stirred at 80° C. for 1 h. The reaction mixture was cooled and concentrated in vacuo. The crude material was purified by preparative HPLC to afford the title compound (5 mg, 56%) as a off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 12.17 (1H, s), 8.31 (1H, d, J=9.6 Hz), 7.95 (1H, s), 7.93 (1H, s), 7.61 (1H, t, J=3.0 Hz), 6.59 (1H, dd, J=1.9, 3.4 Hz), 4.91 (1H, d, J=4.8 Hz), 4.02-3.94 (1H, m), 3.92-3.83 (2H, m), 2.42 (3H, s), 1.16 (3H, d, J=6.3 Hz). LCMS: (M+H)+=358, (M−H)−=356.

後処理

  1. customAn oven dried
  2. customsealed tube
  3. customThe tube was sealed
  4. temperatureThe reaction mixture was cooled
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by preparative HPLC

出典と根拠

ORDレコード
ord-4ad8f1f1c84f449385e65abe0e9d21c2
出典データセット
uspto-grants-2005_11
特許番号
US06969717B2

反応ノート

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