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

HRID 1723689Notes

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]

Participants

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

concentrationwas concentrated in vacuo
washwashed with water
dry with materialThe organic layer was dried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customto give the crude material that
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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