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 1064234Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1064234
[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

Komponenten

4

Edukt 2

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

Produkt 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-olAusbeute 56 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-4ad8f1f1c84f449385e65abe0e9d21c2
Quelldatensatz
uspto-grants-2005_11
Patentnummer
US06969717B2

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