1,3-Dibromo-5,5-dimethylhydantoin → 5-Bromo-6-chloro-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine

HRID 73683Notes

Reaction equation

HRID 73683 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[N:9]([C:10]=1[CH2:11][N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)[N:8]=[CH:7][N:6]=[C:5]2[NH2:18].[Br:19]N1C(C)(C)C(=O)N(Br)C1=O>CN(C=O)C>[Br:19][C:3]1[C:2]([Cl:1])=[C:10]([CH2:11][N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[N:9]2[C:4]=1[C:5]([NH2:18])=[N:6][CH:7]=[N:8]2

Participants

4

Reactant 2

HCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 57955322HCID 57955322, compound

Product 1

HCID 579552265-Bromo-6-chloro-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amineYield 114.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-chloro-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (0.9 g, 3.36 mmol) in DMF (5 mL) at −20° C. was added 1,3-dibromo-5,5-dimethylhydantoin (0.43 g, 1.51 mmol) portion wise over 30 min. The reaction mixture was stirred for 20 minutes at that temperature. TLC analysis indicated that there was complete conversion of starting material. The reaction was quenched with distilled water (30 mL) as the solution warmed to rt. CH2Cl2 (30 mL) was added to the reaction and the solution was transferred to a separatory funnel and the organic layer was isolated while the aqueous layer was back extracted with CH2Cl2 (4×20 mL). The combined organic layers were collected, dried (MgSO4), filtered, and concentrated to dryness. The crude material was washed with diethyl ether (10 mL). The white precipitate was collected and dried under vacuum to yield 0.6 g of the above compound (1.73 mmol, yield 51%). 1H-NMR (CD3OD-d4) δ 7.94 (s, 1H), 3.79 (s, 2H), 3.05 (t, J=4.8 Hz, 4H), 2.39 (t, J=4.8 Hz, 4H); MS [M+H]+=347.7; LCMS RT=1.21 min.

Workup

  1. customThe reaction was quenched with distilled water (30 mL) as the solution
  2. additionCH2Cl2 (30 mL) was added to the reaction
  3. customthe solution was transferred to a separatory funnel
  4. customthe organic layer was isolated while the aqueous layer
  5. extractionwas back extracted with CH2Cl2 (4×20 mL)
  6. customThe combined organic layers were collected
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. washThe crude material was washed with diethyl ether (10 mL)
  11. customThe white precipitate was collected
  12. customdried under vacuum

Sources & evidence

ORD record
ord-d9f766091ee84627b23327107c6f4a69
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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