2-(4-Amino-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl)-cyclopropanecarboxylic acid ethyl ester → 2-(4-Amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl)-cyclopropanecarboxylic acid ethyl ester

HRID 1972876Notes

Reaction equation

HRID 1972876 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:8][CH:7]1[CH2:9][C:10]1[N:18]2[C:13]([C:14]([NH2:19])=[N:15][CH:16]=[N:17]2)=[CH:12][CH:11]=1)=[O:5])[CH3:2].[Br:20]C1C(=O)C(C)(C)C(Br)C1=O>C1COCC1>[CH2:1]([O:3][C:4]([CH:6]1[CH2:8][CH:7]1[CH2:9][C:10]1[N:18]2[C:13]([C:14]([NH2:19])=[N:15][CH:16]=[N:17]2)=[C:12]([Br:20])[CH:11]=1)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 585296522-(4-Amino-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl)-cyclopropanecarboxylic acid ethyl esterHCID 693043752,5-Dibromo-4,4-dimethyl-1,3-cyclopentadione

Product 1

HCID 585297512-(4-Amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl)-cyclopropanecarboxylic acid ethyl esterYield 102.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of 2-(4-amino-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl)-cyclopropanecarboxylic acid ethyl ester (4.5 g, 17.2 mmol) in THF (73 mL) cooled to −20° C. was added 2,5-dibromo-4,4-dimethyl-cyclopentane-1,3-dione (2.4 g, 8.6 mmol) in four portions over 15 mins. The mixture was allowed to stir at −20° C. for 2 hours. The mixture was quenched with sodium thiosulfate solution (20 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (100 mL). The combined organic layer was washed with water, brine, dried by Na2SO4, filtered and concentrated. The residue was purified by Biotage® to give 3.0 g (51%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 7.80 (s, 1 H), 8.75 (bs, 2 H), 6.60 (s, 1 H), 4.0 (m, 2 H), 2.9 (d, 2 H), 1.5 (m, 2 H), 1.2 (t, 3 H), 1.0 (m, 2 H); ES-MS m/z 339.19 [M+H]+, HPLC RT (min) 2.58.

Workup

  1. customThe mixture was quenched with sodium thiosulfate solution (20 mL)
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (100 mL)
  4. washThe combined organic layer was washed with water, brine
  5. dry with materialdried by Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by Biotage®

Sources & evidence

ORD record
ord-2bfefc1a6e5146e9bb853e0141bbbb28
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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