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

HRID 1510563Notes

Reaction equation

HRID 1510563 reaction equation
[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

Participants

8

Reactant 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×

Product 1

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

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-5f88f64372c24412b8ee8482317e4265
Source dataset
uspto-grants-2012_07
Patent number
US08211921B2

Reaction notes

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