Dimethylformamide → 8-(6-amino-4-chloropyridin-2-ylamino)-6-chloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

HRID 1943458

Reaction equation

HRID 1943458 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH2:8])[N:5]=[C:4]([NH2:9])[CH:3]=1.[H-].[Na+].Br[C:13]1[C:14]2[N:15]([C:20]([C:23]([NH:25][C:26]3[CH:31]=[CH:30][N:29]=[CH:28][C:27]=3[F:32])=[O:24])=[CH:21][N:22]=2)[N:16]=[C:17]([Cl:19])[CH:18]=1.CN(C=O)C>C1COCC1.O>[NH2:8][C:6]1[N:5]=[C:4]([NH:9][C:13]2[C:14]3[N:15]([C:20]([C:23]([NH:25][C:26]4[CH:31]=[CH:30][N:29]=[CH:28][C:27]=4[F:32])=[O:24])=[CH:21][N:22]=3)[N:16]=[C:17]([Cl:19])[CH:18]=2)[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 2378474-Chloropyridine-2,6-diamineHCID 596244958-Bromo-6-chloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

Product 1

HCID 596243518-(6-amino-4-chloropyridin-2-ylamino)-6-chloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamideYield 78.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-chloropyridine-2,6-diamine (35.2 mg, 0.245 mmol) in THF (0.5 mL) was added 60% NaH (12.26 mg, 0.307 mmol). The mixture was stirred for 10 min. 5A (40 mg, 0.123 mmol) was added, followed by DMF (0.5 mL). The mixture was stirred at room temperature for 1 h. Water was added and the precipitated solid was collected by filtration, and dried to give crude 40A (42 mg, 59%). HPLC Rt=3.131 min (Chromolith SpeedROD 4.6×50 mm, 10-90% aqueous methanol containing 0.1% TFA, 4 min gradient, monitored at 220 nm), [M+H]=433.

Workup

  1. stirringThe mixture was stirred at room temperature for 1 h
  2. filtrationthe precipitated solid was collected by filtration
  3. customdried

Sources & evidence

ORD record
ord-f237d288611a4f8ca0d4b323f3981078
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Linked notes

Loading…