2,5-Dibromo-4,4-dimethyl-1,3-cyclopentadione → [3-(4-Amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-benzyl]-carbamic acid tert-butyl ester

HRID 1972758Notes

Reaction equation

HRID 1972758 reaction equation
[C:1]([O:5][C:6](=[O:25])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[N:23]3[C:18]([C:19]([NH2:24])=[N:20][CH:21]=[N:22]3)=[CH:17][CH:16]=2)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[Br:26]C1C(=O)C(C)(C)C(Br)C1=O>C1COCC1>[C:1]([O:5][C:6](=[O:25])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[N:23]3[C:18]([C:19]([NH2:24])=[N:20][CH:21]=[N:22]3)=[C:17]([Br:26])[CH:16]=2)[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 693043752,5-Dibromo-4,4-dimethyl-1,3-cyclopentadioneHCID 71134144[3-(4-Amino-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-benzyl]-carbamic acid tert-butyl ester

Product 1

HCID 71134129[3-(4-Amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-benzyl]-carbamic acid tert-butyl esterYield 146.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of [3-(4-amino-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-benzyl]-carbamic acid tert-butyl ester (3.3 g, 9.7 mmol) in THF (73 mL) cooled to −20° C. (isopropanol/ice/CO2), 2,5-dibromo-4,4-dimethyl-cyclopentane-1,3-dione (1.4 g, 4.9 mmol) was added 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 Biatage® to give desired product 3 g (72%). NMR (300 MHz, DMSO-d5) δ 7.80-7.7 (m, 3 H), 7.5 (m, 2 H), 7.2 (m, 2 H), 4.0 (m, 2 H), 1.5 (s, 9 H); ES-MS m/z 420 [M+H]+, HPLC RT (min) 2.91.

Workup

  1. additionwas added in four portions over 15 mins
  2. customThe mixture was quenched with sodium thiosulfate solution (20 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (100 mL)
  5. washThe combined organic layer was washed with water, brine
  6. dry with materialdried by Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by Biatage®

Sources & evidence

ORD record
ord-7df4aee0a4d34f13b3a15905e1cf3e2c
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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