Oxalyl chloride → 4,5-Dihydro-6-oxa-1-thia-3-aza-benzo[e]azulene-2-carboxylic acid (2-chloro-phenyl)-methyl-amide

HRID 1949879

Reaction equation

HRID 1949879 reaction equation
[S:1]1[C:10]2[C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[O:7][CH2:6][CH2:5][C:4]=2[N:3]=[C:2]1[C:15]([OH:17])=O.C(Cl)(=O)C(Cl)=O.[Cl:24][C:25]1[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=1[NH:27][CH3:28]>C(Cl)Cl.CN(C=O)C>[Cl:24][C:25]1[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=1[N:27]([CH3:28])[C:15]([C:2]1[S:1][C:10]2[C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[O:7][CH2:6][CH2:5][C:4]=2[N:3]=1)=[O:17]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 136736Benzenamine, 2-chloro-N-methyl-HCID 866348484,5-Dihydro-6-oxa-1-thia-3-aza-benzo[e]azulene-2-carboxylic acid

Product 1

HCID 579004944,5-Dihydro-6-oxa-1-thia-3-aza-benzo[e]azulene-2-carboxylic acid (2-chloro-phenyl)-methyl-amideYield 30%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 4,5-dihydro-6-oxa-1-thia-3-aza-benzo[e]azulene-2-carboxylic acid (1 eq, 0.38 mmol, 101 mg) in anhydrous DCM (3 ml), 1 drop of DMF was added, followed by 2M oxalyl chloride in DCM (1.7 eq, 0.65 mmol, 330 ul) dropwise. Effervescence was seen and the reaction was stirred at room temperature for 40 mins before evaporating in vacuo. The crude material was dissolved in DCM (3 ml) and 2-chloro-N-methyl aniline (2 eq, 0.76 mmol, 94 ul) was added. The reaction was stirred at room temperature for 16 hr and extracted into DCM, washed with aq K2CO3, the organic layer dried over MgSO4, filtered, and purified on silica (ISCO, gradient 0% ethyl acetate/petrol to 25% ethyl acetate/petrol) to give 326 as a white solid (42 mg, yield 30%). 1H NMR DMSO, 2.89-2.92 (2H, m), 3.43 (3H, s), 4.23 (2H, br. m), 7.02 (1H, d, J=8.4), 7.08 (1H, t, J=7.6), 7.26 (1H, t, J=8), 7.38-7.41 (2H, m), 7.48-7.51 (2H, m), 7.58 (1H, d, J=8.4). MS: (ESI+): MH+ 371, purity >95%.

Workup

  1. additionwas added
  2. custombefore evaporating in vacuo
  3. dissolutionThe crude material was dissolved in DCM (3 ml)
  4. stirringThe reaction was stirred at room temperature for 16 hr
  5. extractionextracted into DCM
  6. washwashed with aq K2CO3
  7. dry with materialthe organic layer dried over MgSO4
  8. filtrationfiltered
  9. custompurified on silica (ISCO, gradient 0% ethyl acetate/petrol to 25% ethyl acetate/petrol)

Sources & evidence

ORD record
ord-7b098a56c17949d49a1e5b2707050a55
Source dataset
uspto-grants-2013_03
Patent number
US08399690B2

Linked notes

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