Hydrochloric Acid → HCID 69021870, compound

HRID 1865138Notes

Reaction equation

HRID 1865138 reaction equation
[C:1]([C:3]1[C:4]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[F:28])=[CH:16][CH:15]=2)=[C:5]([C:11](O)=O)[N:6]([CH3:10])[C:7]=1[CH2:8][CH3:9])#[N:2].[CH3:29][S:30]([NH2:33])(=[O:32])=[O:31].Cl.[CH3:35]N(C)CCCN=C=NCC.Cl>CN(C)C1C=CN=CC=1.C(Cl)Cl>[C:1]([C:3]1[C:4]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[F:28])=[CH:16][CH:15]=2)=[C:5]([C:11]([NH:33][S:30]([CH3:29])(=[O:32])=[O:31])=[CH2:35])[N:6]([CH3:10])[C:7]=1[CH2:8][CH3:9])#[N:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69020394HCID 69020394, compound

Product 1

HCID 69021870HCID 69021870, compoundYield 60.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Mix together 4-cyano-5-ethyl-3-[4-(2-fluoro-benzyloxy)-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid (100 mg, 0.26 mmol, prepared in example A-171), methanesulfonamide (27 mg, 1.1 Eq.), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (60 mg, 1.2 Eq.), and 4-dimethylaminopyridine (35 mg, 1.1 Eq.) in methylene chloride (8 mL) and stir overnight at room temperature under a nitrogen atmosphere. Pour the mixture into 1N HCl and extract the desired amide into methylene chloride. Separate layers, wash the organic layer once with water, dry over anhydrous magnesium sulfate, filter, and concentrate under reduced vacuum to provide 107 mg as an oil. Purify the material by silica gel chromatography (Chromatotron™) eluting with methylene chloride/methanol 19:1 to provide 71 mg of the title compound as a tan foam: Mass spectrum (m/e): 456.2 (M*+1): (Bruker 300) 1H NMR (DMSO) 8.70-8.75 (1H, s), 7.50-7.65 (2H, d), 7.00-7.40 (6H, m), 5.05-5.20 (2H, s), 3.65-3.75 (3H, s), 3.45-3.60 (3H, s), 2.56-2.76 (2H, dd), 1.00-1.10 (3H, t).

Workup

  1. extractionextract the desired amide into methylene chloride
  2. washSeparate layers, wash the organic layer once with water
  3. dry with materialdry over anhydrous magnesium sulfate
  4. filtrationfilter
  5. concentrationconcentrate under reduced vacuum
  6. customto provide 107 mg as an oil
  7. customPurify the material by silica gel chromatography (Chromatotron™)
  8. washeluting with methylene chloride/methanol 19:1

Sources & evidence

ORD record
ord-542a9b16aab64b63b2f430cd528b1f51
Source dataset
uspto-grants-2009_12
Patent number
US07625932B2

Reaction notes

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