Oxalyl chloride → (10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-(2'-methoxy-2-methyl-[1,1'-biphenyl]-4-yl)-methanone

HRID 639266Notes

Reaction equation

HRID 639266 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15]([OH:17])=O)=[CH:11][C:10]=1[CH3:18].C(Cl)(=O)C(Cl)=O.[CH:25]1[CH:26]=[CH:27][N:28]2[CH2:34][C:33]3[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=3[NH:31][CH2:30][C:29]=12.C(N(CC)C(C)C)(C)C>ClCCl.CN(C)C=O>[CH:25]1[CH:26]=[CH:27][N:28]2[CH2:34][C:33]3[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=3[N:31]([C:15]([C:12]3[CH:13]=[CH:14][C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[C:10]([CH3:18])[CH:11]=3)=[O:17])[CH2:30][C:29]=12

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 1554704810,11-Dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepineHCID 219477594-(2-Methoxyphenyl)-3-methylbenzoic acid

Product 1

HCID 21947842(10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-(2'-methoxy-2-methyl-[1,1'-biphenyl]-4-yl)-methanoneYield 99.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×

Procedure

To a stirred solution of 2′-methoxy-2-methyl-biphenyl-4-carboxylic acid (0.250 g; 1.032 mmol) in dichloromethane (20 mL) was added one drop of N,N-dimethylformamide followed by dropwise addition of oxalyl chloride (0.144 mL; 1.65 mmol). After stirring for one hour, the mixture was thoroughly evaporated to give the crude acid chloride as a brown oil. The acid chloride then was dissolved in dichloromethane (5 mL) and slowly added to a solution of 10,11-dihydro-5H-pyrrolo [2,1-c][1,4] benzodiazepine (0.57 g, 3.10 mmol) and N,N-diisopropylethyl amine (0.79 mL, 4.53 mmol) in dichloromethane (15 mL). After stirring for 1 hour, the reaction was quenched with water. The organic layer was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow foam. Purification by flash chromatography using a solvent gradient of 5 to 15% ethyl acetate in hexane yielded a white foam which crystallized upon sonication in ethanol/hexane to give 0.42 g of the desired title product as a white solid, m.p. 133-135° C. MS [(+)ESI, m/z]: 409 [M+H]+. Anal. Calcd. for C27H24N2O2: C, 79.39; H, 5.92; N, 6.86. Found: C, 79.16; H, 5.87; N, 6.90.

Workup

  1. customthe mixture was thoroughly evaporated
  2. customto give the crude acid chloride as a brown oil
  3. stirringAfter stirring for 1 hour
  4. customthe reaction was quenched with water
  5. washThe organic layer was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a yellow foam
  10. customPurification by flash chromatography
  11. customyielded a white foam which
  12. customcrystallized upon sonication in ethanol/hexane

Sources & evidence

ORD record
ord-98e4647dc5e04de99ca81e5fb091a72f
Source dataset
uspto-grants-2010_04
Patent number
US07691848B2

Reaction notes

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