1,3-Dibromo-5,5-dimethylhydantoin → HCID 58529320, compound

HRID 1972773Notes

Reaction equation

HRID 1972773 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[C:12]([C:14]3[N:22]4[C:17]([C:18]([NH2:23])=[N:19][CH:20]=[N:21]4)=[CH:16][CH:15]=3)[CH:11]=[CH:10][N:9]=2)[CH2:4][CH2:3]1.[Br:24]N1C(C)(C)C(=O)N(Br)C1=O>O1CCCC1>[Br:24][C:16]1[CH:15]=[C:14]([C:12]2[CH:11]=[CH:10][N:9]=[C:8]([N:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)[CH:13]=2)[N:22]2[C:17]=1[C:18]([NH2:23])=[N:19][CH:20]=[N:21]2

Participants

4

Reactant 2

HCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 58529634HCID 58529634, compound

Product 1

HCID 58529320HCID 58529320, compoundYield 38.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a cooled (−20° C.) solution 7-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-4-amine (250 mg, 0.81 mmol) in tetrahydrofuran (5 mL) was added 1,3-dibromo-5,5-dimethylhydantoin (115 mg, 0.40 mmol) in four portions over 15 min. The mixture was allowed to stir (−20° C.) for 4 h. The reaction was quenched with the addition saturated aqueous Na2SO3 (10 mL) and was allowed to warm to rt. The mixture was extracted with ethyl acetate (2×20 mL). The combined organics were filtered to remove a fine precipitate and the filtrate was washed with brine, dried (Na2SO4) and concentrated. The residue was purified by preparative HPLC using a gradient elution from 0% to 25% acetonitrile in water to obtain 60 mg (19%) of the desired product as a yellow foam. 1H NMR (300 MHz, DMSO-d6) δ 8.70 (d, 1 H), 8.14 (dd, 1 H), 7.89 (s, 1 H), 7.14 (s, 1 H), 6.90 (d, 1 H), 3.55-3.50 (m, 4 H), 2.40-2.34 (m, 4 H), 2.20 (s, 3 H); ES-MS m/z 388.12 [M+H]+, HPLC RT (min) 1.38.

Workup

  1. customThe reaction was quenched with the addition saturated aqueous Na2SO3 (10 mL)
  2. temperatureto warm to rt
  3. extractionThe mixture was extracted with ethyl acetate (2×20 mL)
  4. filtrationThe combined organics were filtered
  5. customto remove a fine precipitate
  6. washthe filtrate was washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe residue was purified by preparative HPLC
  10. washa gradient elution from 0% to 25% acetonitrile in water

Sources & evidence

ORD record
ord-14b8511d86dd4218a6267cb098e2a9ea
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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