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 1064234Notes

Reaction equation

[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

Participants

Conditions

Temperature: 80 °C

Procedure

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.

Workup

customAn oven dried
customsealed tube
customThe tube was sealed
temperatureThe reaction mixture was cooled
concentrationconcentrated in vacuo
customThe crude material was purified by preparative HPLC

Sources & evidence

ORD record: ord-4ad8f1f1c84f449385e65abe0e9d21c2
Source dataset: uspto-grants-2005_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06969717B2

Reaction notes

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