N-bromobutanimide → 5-Bromo-6-chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

HRID 2044061Notes

Reaction equation

HRID 2044061 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])=[CH:14][CH:13]=2)[N:3]=1.C1C(=O)N([Br:33])C(=O)C1.OS([O-])=O.[Na+]>C(#N)C.C(OCC)(=O)C>[Br:33][C:10]1[C:2]([Cl:1])=[N:3][C:4]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]([N:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]3)=[O:19])=[CH:16][CH:17]=2)=[C:5]([CH:9]=1)[C:6]([NH2:8])=[O:7]

Participants

6

Reactant 3

HCID 67184N-bromobutanimideHCID 23665763Sodium BisulfiteHCID 574896016-Chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

Product 1

HCID 574896165-Bromo-6-chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamideYield 38.6%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 6-chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide (500 mg, 1.385 mmol) and NBS (250 mg, 1.4 mmol) in acetonitrile (10 mL) was stirred at overnight. The reaction mixture was treated with 1M NaHSO3 and stirred at rt for 2 h. Next, the reaction mixture was diluted with ethyl acetate and the precipitate filtered to give a solid. The organic layer of the filtrate was separated and concentrated to an additional amount of solid. The above solids were combined and triturated with 250 mL of MeOH/CH2Cl2 (˜1:1 ratio) to give 235 mg of 5-bromo-6-chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide as a grey solid. LCMS: (M+H)+=338.80, 440.83, 442.87 (Br, Cl pattern). 1H NMR (400 MHz, methanol-d3-MIX) δ ppm 8.38 (1H, s), 7.77 (2H, d, J=8.35 Hz), 7.42 (2H, d, J=8.79 Hz), 3.69 (8H, br. s.).

Workup

  1. stirringstirred at rt for 2 h
  2. filtrationthe precipitate filtered
  3. customto give a solid
  4. customThe organic layer of the filtrate was separated
  5. concentrationconcentrated to an additional amount of solid
  6. customtriturated with 250 mL of MeOH/CH2Cl2 (˜1:1 ratio)

Sources & evidence

ORD record
ord-a3e815b8d3e747bda3923439036c1aac
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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