Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → 3-((6-Chloro-3-cyanoimidazo[1,2-b]pyridazin-8-yl)(4-methoxybenzyl)amino)-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide

HRID 2206369Notes

Reaction equation

HRID 2206369 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:13]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[C:14]2[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=2)[C:17](O)=[O:18])[C:5]2[N:6]([C:8]([C:11]#[N:12])=[CH:9][N:10]=2)[N:7]=1.[CH3:32][NH:33][CH:34]1[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([N:13]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[C:14]2[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=2)[C:17]([N:33]([CH3:32])[CH:34]2[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35]2)=[O:18])[C:5]2[N:6]([C:8]([C:11]#[N:12])=[CH:9][N:10]=2)[N:7]=1

Participants

5

Reactant 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 2758520N,1-dimethylpyrrolidin-3-amineHCID 593140063-((6-Chloro-3-cyanoimidazo[1,2-b]pyridazin-8-yl)(4-methoxybenzyl)amino)benzoic acid

Product 1

HCID 593140333-((6-Chloro-3-cyanoimidazo[1,2-b]pyridazin-8-yl)(4-methoxybenzyl)amino)-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamideYield 55.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 253C (500 mg, 1.152 mmol) in DMF (1 mL) was treated with N,1-dimethylpyrrolidin-3-amine (0.217 mL, 1.73 mmol), BOP (663 mg, 1.5 mmol) and TEA (0.32 mL, 2.30 mmol), and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was triturated with water, and the solid was collected by filtration and dried in vacuo to obtain 254A (337 mg, 0.636 mmol, 55.2% yield) as a light grey solid. HPLC: Rt=1.56 min. (PHENOMENEX® Luna 5 micron C18 4.6×30 mm, 0 to 100 B in 2 min. with 1 min. hold time, flow rate=5 mL/min., detection at 254 nm, Solvent A: 10% methanol/90% water/0.1% TFA; solvent B: 10% water/90% methanol/0.1% TFA). MS (ES): m/z=531.97 [M+H]+.

Workup

  1. customThe reaction mixture was triturated with water
  2. filtrationthe solid was collected by filtration
  3. customdried in vacuo

Sources & evidence

ORD record
ord-e9ca3033561742a3858536d2801c8e17
Source dataset
uspto-grants-2016_06
Patent number
US09371328B2

Reaction notes

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