1,1'-Carbonyldiimidazole → N-[4-(4-Bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carbonyl]-C-phenyl-methanesulfonamide

HRID 422778ノート

反応式

HRID 422778 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:18]([OH:20])=O)=[CH:11][N:12]([CH3:17])[C:13](=[O:16])[C:14]=2[CH3:15])=[C:4]([F:21])[CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[C:34]1([CH2:40][S:41]([NH2:44])(=[O:43])=[O:42])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C1CCN2C(=NCCC2)CC1>CN(C=O)C.CCOC(C)=O.Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:18]([NH:44][S:41]([CH2:40][C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)(=[O:42])=[O:43])=[O:20])=[CH:11][N:12]([CH3:17])[C:13](=[O:16])[C:14]=2[CH3:15])=[C:4]([F:21])[CH:3]=1

参加物

8

反応物 4

HCID 682631,1'-CarbonyldiimidazoleHCID 78318BenzenemethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 116460904-(4-Bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid2 回

生成物 1

HCID 57636909N-[4-(4-Bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carbonyl]-C-phenyl-methanesulfonamide収率 68%

試薬・触媒・溶媒 3

HCID 313Hydrochloric Acid溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

N-[4-(4-Bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carbonyl]-C-phenyl-methanesulfonamide was prepared from 4-(4-bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid as follows. To a solution of 4-(4-bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (0.040 mg, 0.113 mmol) in DMF (1.5 mL) was added 1,1′-carbonyldiimidazole (0.074 mg, 0.456 mmol). After stirring for two hours, α-toluenesulfonamide (0.079 mg, 0.461 mmol) was added, followed by DBU (0.070 mL, 0.459 mmol). After stirring for 16 hours at room temperature, the reaction mixture was diluted with EtOAc and 1N HCl solution. The organic layer was separated and washed with brine. The aqueous layer was extracted with EtOAc (2×) and washed with brine. The combined organic extracts were dried (MgSO4) and concentrated under reduced pressure. Purification by flash column chromatography (2% MeOH in methylene chloride) gave 0.039 g (68%) clean desired product; MS APCI (−) m/z 506, 508 (M−, Br pattern) detected; 1H NMR (400 MHz, CD3OD) δ 8.29 (s, 1H), 7.27 (m, 3H), 7.18 (d, 1H), 7.11 (m, 3H), 6.56 (t, 1H), 4.44 (s, 2H), 3.54 (s, 3H), 1.62 (s, 3H).

後処理

  1. stirringAfter stirring for 16 hours at room temperature
  2. customThe organic layer was separated
  3. washwashed with brine
  4. extractionThe aqueous layer was extracted with EtOAc (2×)
  5. washwashed with brine
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash column chromatography (2% MeOH in methylene chloride)

出典と根拠

ORDレコード
ord-ce10ea455ea844b29132463b85d1d114
出典データセット
uspto-grants-2012_01
特許番号
US08101639B2

反応ノート

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