Oxalyl chloride → HCID 67287554, compound

HRID 1626533Notes

Reaction equation

HRID 1626533 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.[NH2:33][CH2:34][CH2:35][C:36]1[C:37]([N:45]([CH3:47])[CH3:46])=[N:38][C:39]([CH:42]2[CH2:44][CH2:43]2)=[CH:40][CH:41]=1.C(N(C(C)C)CC)(C)C>ClCCl.CN(C)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:21]=[CH:20][C:16]([C:17](=[O:18])[NH:33][CH2:34][CH2:35][C:36]3[C:37]([N:45]([CH3:46])[CH3:47])=[N:38][C:39]([CH:42]4[CH2:43][CH2:44]4)=[CH:40][CH:41]=3)=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acidHCID 67288108HCID 67288108, compound

Product 1

HCID 67287554HCID 67287554, compoundYield 25.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

4-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation B; 200 mg, 0.531 mmol) was diluted with dichloromethane (2 mL) followed by the addition of oxalyl chloride in dichloromethane (2M) (292 μL, 0.584 mmol) and dimethylformamide (1 drop). After stirring for 15 minutes, 3-(2-aminoethyl)-6-cyclopropyl-N,N-dimethylpyridin-2-amine (109 mg, 0.531 mmol) and diisopropyl ethylamine (277 μL, 1.59 mmol) were added. After stirring for 2 hours, the reaction was loaded onto silica gel and eluted with 5% ethyl acetate/hexanes to 100% ethyl acetate to yield ethyl 6-chloro-7-(4-(2-(6-cyclopropyl-2-(dimethylamino)pyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylate (77 mg, 0.137 mmol, 25.7% yield).

Workup

  1. stirringAfter stirring for 2 hours
  2. washeluted with 5% ethyl acetate/hexanes to 100% ethyl acetate

Sources & evidence

ORD record
ord-f3a9553209504fb1bb2f0c4e88f08c95
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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