Pyridine → 6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid ((R)-1-ethyl-pyrrolidin-2-ylmethyl)-amide

HRID 1972052Notes

Reaction equation

HRID 1972052 reaction equation
Cl.Cl.N1CCOC([CH2:9][NH:10][C:11]([C:13]2[N:14]=[N:15][C:16]([CH2:32][CH2:33][CH2:34][CH3:35])=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]4)=[CH:21][CH:20]=3)[CH:18]=2)=[O:12])C1.N1C=CC=CC=1.[CH2:42]([N:44]1[CH2:48][CH2:47][CH2:46][C@@H:45]1NC)[CH3:43]>C1COCC1>[CH2:42]([N:44]1[CH2:48][CH2:47][CH2:46][C@@H:45]1[CH2:9][NH:10][C:11]([C:13]1[N:14]=[N:15][C:16]([CH2:32][CH2:33][CH2:34][CH3:35])=[C:17]([C:19]2[CH:20]=[CH:21][C:22]([O:25][CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:23][CH:24]=2)[CH:18]=1)=[O:12])[CH3:43]

Participants

5

Reactant 3

HCID 1049PyridineHCID 67372883((R)-1-ethyl-pyrrolidin-2-yl)-methylamineHCID 673737226-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid (morpholin-2-ylmethyl)-amide dihydrochloride

Product 1

HCID 584384156-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid ((R)-1-ethyl-pyrrolidin-2-ylmethyl)-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid pentafluorophenyl ester hydrochloride (Example 90, 0.18 mmol, 0.1 g) and 0.1 mL of pyridine in 2 mL of THF was added ((R)-1-ethyl-pyrrolidin-2-yl)-methylamine (0.4 mmol, 0.05 g). The mixture was shaken at room temperature, upon completion, the solvent was removed and the residue was chromatographed with 4% methanolic solution of ammonia (2.0 M ammonia in methanol) in EtOAc afforded 6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid ((R)-1-ethyl-pyrrolidin-2-ylmethyl)-amide. LCMS: m/z 464.9. 1H NMR (400 MHz, CD3OD) δ 8.27 (1H, s), 7.42 (2H, d), 7.09 (2H, d), 4.44-4.40 (1H, m), 4.00-3.96 (1H, m), 3.80-3.68 (4H, m), 3.20-3.10 (4H, m), 2.34-2.28 (1H, m), 2.16-2.02 (5H, m), 1.84-1.80 (2H, m), 1.64-1.27 (13H, m), 0.83 (3H, t).

Workup

  1. customthe solvent was removed
  2. customthe residue was chromatographed with 4% methanolic solution of ammonia (2.0 M ammonia in methanol) in EtOAc

Sources & evidence

ORD record
ord-ec9bba89d3b24105bd7567b6c2fcedca
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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