6-Amino-3-chloropyridazine → HCID 86664394, compound

HRID 1626436Notes

Reaction equation

HRID 1626436 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23].C(Cl)(=O)C(Cl)=O.[Cl:33][C:34]1[N:39]=[N:38][C:37]([NH2:40])=[CH:36][CH:35]=1>ClCCCl.CN(C=O)C.N1C=CC=CC=1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:14]=[CH:15][C:16]([C:17](=[O:18])[NH:40][C:37]3[N:38]=[N:39][C:34]([Cl:33])=[CH:35][CH:36]=3)=[CH:20][CH:21]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23]

Participants

8

Reactant 3

HCID 216436-Amino-3-chloropyridazineHCID 65578Oxalyl chlorideHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid

Product 1

HCID 86664394HCID 86664394, compoundYield 77.1%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 111,2-DichloroethaneSolventHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation B; 0.500 g, 1.334 mmol) in 1,2-dichloroethane (1.3 ml) and DMF (1 drop) was added oxalyl chloride (0.1396 ml, 1.601 mmol), and the reaction was stirred for 1 hour at ambient temperature. The reaction was diluted with pyridine (5 ml) and 6-chloropyridazin-3-amine (0.2592 g, 2.001 mmol) was added. The reaction was heated to 80° C. for 16 hours, then diluted with EtOAc and washed with 1M hydrochloric acid, sodium bicarbonate, and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was purified by silica gel chromatography eluting with a linear gradient of 5-70% EtOAc/hexanes to yield the desired compound (0.5 g, 1.028 mmol, 77.07% yield).

Workup

  1. additionwas added
  2. temperatureThe reaction was heated to 80° C. for 16 hours
  3. washwashed with 1M hydrochloric acid, sodium bicarbonate, and saturated sodium chloride
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel chromatography
  8. washeluting with a linear gradient of 5-70% EtOAc/hexanes

Sources & evidence

ORD record
ord-0538a85bc3c6477f86ff772f90a1c20b
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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