3,4-Dichloroaniline → methyl 7-(4-((3,4-dichlorophenyl)carbamoyl)phenoxy)-6-cyano-3,4-dihydro-2H-chromene-4-carboxylate

HRID 510614Notes

Reaction equation

HRID 510614 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][C:14]1[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=1)[O:9][CH2:8][CH2:7][CH:6]2[C:23]([O:25][CH3:26])=[O:24])#[N:2].C(Cl)(=O)C(Cl)=O.[Cl:33][C:34]1[CH:35]=[C:36]([NH2:41])[CH:37]=[CH:38][C:39]=1[Cl:40].C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C=O)C>[Cl:33][C:34]1[CH:35]=[C:36]([NH:41][C:18]([C:17]2[CH:16]=[CH:15][C:14]([O:13][C:12]3[CH:11]=[C:10]4[C:5]([CH:6]([C:23]([O:25][CH3:26])=[O:24])[CH2:7][CH2:8][O:9]4)=[CH:4][C:3]=3[C:1]#[N:2])=[CH:22][CH:21]=2)=[O:19])[CH:37]=[CH:38][C:39]=1[Cl:40]

Participants

7

Reactant 4

HCID 72573,4-DichloroanilineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 462211084-(6-Cyano-4-(methoxycarbonyl)-chroman-7-yloxy)benzoic acid

Product 1

HCID 67080311methyl 7-(4-((3,4-dichlorophenyl)carbamoyl)phenoxy)-6-cyano-3,4-dihydro-2H-chromene-4-carboxylateYield 71.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

4-(6-Cyano-4-(methoxycarbonyl)-3,4-dihydro-2H-chromen-7-yloxy)benzoic acid (17 mg, 0.0481 mmol) was diluted with CH2Cl2 (1 mL) followed by the addition of oxalyl chloride in CH2Cl2 (2M in CH2Cl2) (0.0289 mL, 0.0577 mmol) and 1 drop of DMF. The reaction was stirred for 20 minutes, and then 3,4-dichlorobenzenamine (15.6 mg, 0.0962 mmol) and N,N-diisopropylethylamine (0.0210 mL, 0.120 mmol) were added. After stirring for 30 minutes the reaction was loaded directly onto a Biotage 12i eluting with hexane:ethyl acetate (1:1) to yield the title compound (17 mg, 71.0% yield) as a clear oil.

Workup

  1. stirringAfter stirring for 30 minutes the reaction
  2. washeluting with hexane:ethyl acetate (1:1)

Sources & evidence

ORD record
ord-d08085219c78410bae68111643da826b
Source dataset
uspto-grants-2015_08
Patent number
US09096567B2

Reaction notes

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