Azetidine → 4-(5-(azetidine-1-carbonyl)pyridin-2-ylamino)-6-chloro-2-methylpyridazin-3(2H)-one

HRID 1431156Notes

Reaction equation

HRID 1431156 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.C(Cl)(=O)C(Cl)=O.[NH:26]1[CH2:29][CH2:28][CH2:27]1.CCN(C(C)C)C(C)C>ClCCl.CN(C=O)C>[N:26]1([C:15]([C:14]2[CH:18]=[CH:19][C:11]([NH:10][C:4]3[C:5](=[O:9])[N:6]([CH3:8])[N:7]=[C:2]([Cl:1])[CH:3]=3)=[N:12][CH:13]=2)=[O:17])[CH2:29][CH2:28][CH2:27]1

Participants

7

Reactant 4

HCID 10422AzetidineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 667425116-(6-Chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)nicotinic acid

Product 1

HCID 667429454-(5-(azetidine-1-carbonyl)pyridin-2-ylamino)-6-chloro-2-methylpyridazin-3(2H)-oneYield 127.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)nicotinic acid (100 mg, 356 μmol, Eq: 1.00) was suspended in dichloromethane. Oxalyl chloride (67.8 mg, 46.8 μl, 534 μmol, Eq: 1.5) was added followed by a drop of DMF (10 μl) and the reaction mixture was stirred for 2 hr at room temperature. The reaction mixture was concentrated. The acid chloride was used as is for the next step. It was dissolved in dichloromethane (10 ml). To that was added azetidine (20.3 mg, 24.0 μl, 356 μmol, Eq: 1.00) followed by DIEA (230 mg, 311 μl, 1.78 mmol, Eq: 5) and the reaction was stirred over night at room temperature. The reaction mixture was diluted with dichloromethane, washed with a saturated sodium carbonate solution, washed with brine, dried over sodium sulfate, filtered and concentrated to give a light brown solid (145 mg) which was triturated with DCM/Hex/EtOAc to give the desired product as a yellow solid (56 mg). (M+H)+=320.0 m/e

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionIt was dissolved in dichloromethane (10 ml)
  3. stirringthe reaction was stirred over night at room temperature
  4. washwashed with a saturated sodium carbonate solution
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-6bebec75aa0e46018dbd9fa1a231806b
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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