Ethyl Acetate → 1-(3,4-Dichlorophenyl)-6-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)-1,6-dihydropyridazine-3-carboxylic acid

HRID 386560Notes

Reaction equation

HRID 386560 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([N:10]2[C:15](=[O:16])[CH:14]=[C:13]([O:17][CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[C:12]([C:24]([OH:26])=[O:25])=[N:11]2)[CH:6]=[CH:7][C:8]=1[Cl:9].CCN(C(C)C)C(C)C.Cl[C:37]1[N:42]=[CH:41][C:40]([CH2:43][CH2:44][CH3:45])=[CH:39][N:38]=1.CCOC(C)=O>CN1C(=O)CCC1>[Cl:2][C:3]1[CH:4]=[C:5]([N:10]2[C:15](=[O:16])[CH:14]=[C:13]([O:17][CH:18]3[CH2:19][CH2:20][N:21]([C:37]4[N:42]=[CH:41][C:40]([CH2:43][CH2:44][CH3:45])=[CH:39][N:38]=4)[CH2:22][CH2:23]3)[C:12]([C:24]([OH:26])=[O:25])=[N:11]2)[CH:6]=[CH:7][C:8]=1[Cl:9]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 27357842-Chloro-5-propylpyrimidineHCID 670726151(3,4-dichlorophenyl)-6-oxo-4-(piperidin-4-yloxy)-1,6-dihydropyridazine-3-carboxylic acid HCl salt

Product 1

HCID 670725321-(3,4-Dichlorophenyl)-6-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)-1,6-dihydropyridazine-3-carboxylic acidYield 52.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirring solution of 1-(3,4-dichlorophenyl)-6-oxo-4-(piperidin-4-yloxy)-1,6-dihydropyridazine-3-carboxylic acid HCl (83 mg, 0.217 mmol) in NMP (2 mL) at room temperature under argon was added DIPEA (84 mg, 0.651 mmol) and 2-chloro-5-propylpyrimidine (51 mg, 0.326 mmol). The resulting reaction mixture was heated at 100° C. under argon overnight. 15 mL of EtOAc was added to the reaction mixture. The reaction mixture was washed with water (15 mL), and brine (15 mL). Organic phase was dried (MgSO4), filtered and concentrated. The crude product was directly purified by preparative HPLC (C18 column; 10-100% methanol in water without TFA) to give 1-(3,4-dichlorophenyl)-6-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)-1,6-dihydropyridazine-3-carboxylic acid (57 mg, white solid, 52%). MS (ESI) 504 (M+H).

Workup

  1. customThe resulting reaction mixture
  2. washThe reaction mixture was washed with water (15 mL), and brine (15 mL)
  3. dry with materialOrganic phase was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was directly purified by preparative HPLC (C18 column; 10-100% methanol in water without TFA)

Sources & evidence

ORD record
ord-e18534cddb824bc9b4aaebe38865f7ec
Source dataset
uspto-grants-2013_02
Patent number
US08372837B2

Reaction notes

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