Water → 6-Fluoro-pyridine-2-carboxylic acid (6-chloro-4-propyl-pyridazin-3-ylmethyl)-isobutyl-amide

HRID 898697Notes

Reaction equation

HRID 898697 reaction equation
[Cl:1][C:2]1[N:7]=[N:6][C:5]([CH2:8][NH:9][CH2:10][CH:11]([CH3:13])[CH3:12])=[C:4]([CH2:14][CH2:15][CH3:16])[CH:3]=1.[F:17][C:18]1[N:23]=[C:22]([C:24](O)=[O:25])[CH:21]=[CH:20][CH:19]=1.CCN=C=NCCCN(C)C.O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[N:7]=[N:6][C:5]([CH2:8][N:9]([CH2:10][CH:11]([CH3:12])[CH3:13])[C:24]([C:22]2[CH:21]=[CH:20][CH:19]=[C:18]([F:17])[N:23]=2)=[O:25])=[C:4]([CH2:14][CH2:15][CH3:16])[CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 2260276-Fluoropyridine-2-carboxylic acidHCID 58661541(6-Chloro-4-propyl-pyridazin-3-ylmethyl)-isobutyl-amine

Product 1

HCID 586615406-Fluoro-pyridine-2-carboxylic acid (6-chloro-4-propyl-pyridazin-3-ylmethyl)-isobutyl-amide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (6-chloro-4-propyl-pyridazin-3-ylmethyl)-isobutyl-amine (940 mg, 3.89 mmol) and 6-fluoro-pyridine-2-carboxylic acid (663 mg, 4.7 mmol) in CH2Cl2 (10 ml) is added EDCI (783 mg, 4.7 mmol) and DMAP (244 mg, 2 mmol). The mixture is stirred at room temperature overnight. Water (10 ml) is added and the layers are separated. The organic layer is washed with brine (10 ml), then dried (Na2SO4) and evaporated. Flash column purification of the residue (2:1 of hexane: ethyl acetate) provides the title product. 1H NMR (CDCl3) (mixture of rotamers) 7.89 (q, 0.7H), 7.81 (q, 0.3H), 7.69 (dd, 0.3H), 7.53 (dd, 0.7H), 7.34 (s, 0.7H), 7.20 (s, 0.3H), 6.99 (dd, 0.7H1), 6.91 (dd, 0.3H), 5.19 (s, 0.6H), 5.07 (s, 1.4H), 3.41 (d, 0.6H), 3.31 (d, 1.4H1), 2.75 (t, 1.4H1), 2.48 (t, 0.6H), 2.08-2.17 (m, 1H), 1.69-1.75 (m, 1.4H1), 1.54-1.60 (m, 0.6H), 1.02 (t, 2.11H), 0.99 (d, 1.8H), 0.97 (t, 0.9H), 0.80 (d, 4.2H).

Workup

  1. customthe layers are separated
  2. washThe organic layer is washed with brine (10 ml)
  3. dry with materialdried (Na2SO4)
  4. customevaporated
  5. customFlash column purification of the residue (2:1 of hexane: ethyl acetate)

Sources & evidence

ORD record
ord-c947a1a0508e4a35b19304f076134bc1
Source dataset
uspto-grants-2008_04
Patent number
US07351826B2

Reaction notes

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