Dimethylformamide → 2-Chloro-6-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-N-(methylsulfonyl)pyrimidine-4-carboxamide

HRID 2233995Notes

Reaction equation

HRID 2233995 reaction equation
[CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].[H-].[Na+].[Cl:8][C:9]1[NH:14][C:13]([N:19]2[CH2:24][CH2:23][CH:22]([NH:25][C:26]([C:28]3[NH:29][C:30]([CH3:35])=[C:31]([Cl:34])[C:32]=3[Cl:33])=[O:27])[CH2:21][CH2:20]2)(C(OC)=O)[CH:12]=[CH:11][N:10]=1.CN([CH:39]=[O:40])C>>[Cl:8][C:9]1[N:10]=[C:11]([C:39]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])=[O:40])[CH:12]=[C:13]([N:19]2[CH2:24][CH2:23][CH:22]([NH:25][C:26]([C:28]3[NH:29][C:30]([CH3:35])=[C:31]([Cl:34])[C:32]=3[Cl:33])=[O:27])[CH2:21][CH2:20]2)[N:14]=1

Participants

5

Reactant 4

HCID 6228Dimethylformamide3×HCID 24758Sodium hydrideHCID 72879MethanesulfonamideHCID 178499026HCID 178499026, compound

Product 1

HCID 866083372-Chloro-6-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-N-(methylsulfonyl)pyrimidine-4-carboxamide

Procedure

A solution of methanesulfonamide (40 mg, 0.44 mmol) and DMF (0.5 ml) was added to a suspension of sodium hydride (95%) (11 mg, 0.44 mmol) and DMF (0.5 ml) under nitrogen. The mixture was stirred for 20 minutes at room temperature. A solution of methyl 2-chloro-6-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)pyrimidine-4-carboxylate (Example 6, 47 mg, 0.11 mmol) in DMF (1 ml) was added dropwise to the mixture over 5 minutes. The mixture was stirred for 1 h at room temperature and for 3 h at 60° C. The mixture was cooled to room temperature and concentrated under reduced pressure. The crude residue was purified by preparative reversed-phase HPLC (water/acetonitrile gradient, 10-90%) to afford the title compound (14 mg).

Workup

  1. stirringThe mixture was stirred for 1 h at room temperature and for 3 h at 60° C
  2. temperatureThe mixture was cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. customThe crude residue was purified by preparative reversed-phase HPLC (water/acetonitrile gradient, 10-90%)

Sources & evidence

ORD record
ord-b9d6d904d60b41438076fa93fbdb66d3
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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