Sodium Iodide → 5-Bromo-7-(4-pyrrolidin-1-ylbutyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine

HRID 1972782Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([CH2:12][CH2:13][CH2:14][CH2:15]Br)[N:5]2[C:10]=1[C:9]([NH2:11])=[N:8][CH:7]=[N:6]2.[NH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1.C(N(CC)CC)C.[I-].[Na+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH2:12][CH2:13][CH2:14][CH2:15][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[N:5]2[C:10]=1[C:9]([NH2:11])=[N:8][CH:7]=[N:6]2

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of 5-bromo-7-(4-bromobutyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (597 mg, 1.72 mmol) in DMF (10 mL) was added pyrrolidine (158 μL, 1.89 mmol), triethylamine (717 μL, 5.15 mmol), and sodium iodide (26 mg, 0.17 mmol). The reaction was heated (55° C.) for 22 h and then cooled to rt. The mixture was partitioned between ethyl acetate (50 mL) and water (50 mL). The layers were separated and the aqueous phase was further extracted with ethyl acetate (3×50 mL). The combined organics were washed with water (1×50 mL), brine, dried (Na2SO4) and evaporated to afford 467 mg (80%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 7.81 (s, 1 H), 6.60 (s, 1 H), 2.81 (t, 2 H), 2.40-2.31 (m, 6 H), 1.70-1.59 (m, 6 H), 1.50-1.40 (m, 2 H); ES-MS m/z 338.1 [M+H]+, HPLC RT (min) 1.12.

Workup

temperaturecooled to rt
customThe mixture was partitioned between ethyl acetate (50 mL) and water (50 mL)
customThe layers were separated
extractionthe aqueous phase was further extracted with ethyl acetate (3×50 mL)
washThe combined organics were washed with water (1×50 mL), brine
dry with materialdried (Na2SO4)
customevaporated

Sources & evidence

ORD record: ord-f5baaf5a47a548b1a23956c260bfa415
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431695B2

Reaction notes

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