Dimethylformamide → HCID 67290174, compound

HRID 1626520Notes

Reaction equation

HRID 1626520 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]([OH:19])=O)=[CH:15][CH:14]=1)O[CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23].[C:27](Cl)(=O)C(Cl)=O.CN(C=O)C.[F:38][C:39]([F:54])([F:53])[C:40]1[CH:45]=[CH:44][C:43]([C:46]2[N:51]=[N:50][C:49]([NH2:52])=[CH:48][CH:47]=2)=[CH:42][CH:41]=1>ClCCCl.CN(C=O)C.CCOC(C)=O.N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9]([CH2:27][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:10][C:11]=1[O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](=[O:19])[NH:52][C:49]2[N:50]=[N:51][C:46]([C:43]3[CH:42]=[CH:41][C:40]([C:39]([F:38])([F:53])[F:54])=[CH:45][CH:44]=3)=[CH:47][CH:48]=2)=[CH:15][CH:14]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 49758339HCID 49758339, compoundHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid

Product 1

HCID 67290174HCID 67290174, compoundYield 53.9%

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; 2.137 g, 5.701 mmol) in DCE (6 mL) and DMF (1 drop) was added oxalyl dichloride (0.5968 mL, 6.841 mmol), and the reaction was allowed to stir at ambient temperature for 1 hour. The evolution of gases slowed several times, and 3 more drops of DMF were added over the course of this activation step. Pyridine (24 mL) and 6-(4-(trifluoromethyl)phenyl)pyridazin-3-amine (1.5 g, 6.271 mmol) were added, and the reaction was heated to 80° C. overnight. The reaction mixture was diluted with EtOAc and washed with 10% citric acid, sodium bicarbonate and brine. The organic layer was dried over Na2SO4, filtered, and concentrated. The crude material was precipitated from EtOAc/hexanes to yield ethyl 7-chloro-6-(4-(6-(4-(trifluoromethyl)phenyl)pyridazin-3-ylcarbamoyl)phenoxy)-1,2,3,4-tetrahydronaphthalene-1-carboxylate (1.83 g, 3.070 mmol, 53.86% yield). MS (apci, positive) m/z=597.9.

Workup

  1. additionwere added over the course of this activation step
  2. temperaturethe reaction was heated to 80° C. overnight
  3. washwashed with 10% citric acid, sodium bicarbonate and brine
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was precipitated from EtOAc/hexanes

Sources & evidence

ORD record
ord-1ceed8553f234ef5b1fafe8219546ebd
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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