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N-Iodosuccinimide → 8-(2-chloro-4-iodophenylamino)-6,7-difluoro-4-methyl-2H-phthalazin-1-one

HRID 1723689
Notes
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Reaction equation

HRID 1723689 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[C:10]([F:22])=[C:11]([F:21])[CH:12]=[C:13]2[C:18]=1[C:17](=[O:19])[NH:16][N:15]=[C:14]2[CH3:20].C1C(=O)N([I:30])C(=O)C1>CC(O)=O.C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([I:30])[CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[C:10]([F:22])=[C:11]([F:21])[CH:12]=[C:13]2[C:18]=1[C:17](=[O:19])[NH:16][N:15]=[C:14]2[CH3:20]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 120273N-IodosuccinimideHCID 674043668-(2-chlorophenylamino)-6,7-difluoro-4-methyl-2H-phthalazin-1-one

Product 1

HCID 113513368-(2-chloro-4-iodophenylamino)-6,7-difluoro-4-methyl-2H-phthalazin-1-oneYield 18.5%

Reagents, catalysts & solvents 1

HCID 23444217Acetic acid tetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 8-(2-chlorophenylamino)-6,7-difluoro-4-methyl-2H-phthalazin-1-one (30 mg, 0.093 mmol) and NIS (24 mg, 0.11 mmol) in AcOH-THF (2 mL/0.5 mL) was heated at 85° C. for 3 minutes The reaction mixture was concentrated in vacuo and washed with water. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo to give the crude material that was purified by silica gel flash column chromatography (100% hexanes to 15% EtOAc in hexanes) to afford 8-(2-chloro-4-iodophenylamino)-6,7-difluoro-4-methyl-2H-phthalazin-1-one (7.7 mg, 17%). MS APCI (−) m/z 446, 448 (M-, Cl pattern) detected; 1H NMR (400 MHz, DMSO-d6) δ 12.74 (s, 1H), 10.96 (s, 1H), 7.86 (s, 1H), 7.60 (d, 1H), 7.53 (dd, 1H), 6.94 (t, 1H), 2.47 (s, 3H).

Workup

  1. concentrationwas concentrated in vacuo
  2. washwashed with water
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give the crude material that
  7. customwas purified by silica gel flash column chromatography (100% hexanes to 15% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0ed3e2cab4cf43da8664926eba466d1e
Source dataset
uspto-grants-2009_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07485643B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes