Water → HCID 20872400, compound

HRID 497409Notes

Reaction equation

HRID 497409 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:12]=[C:11]([C:13]([O:15][CH3:16])=[O:14])[C:10]2[C:17](=[O:22])[CH2:18][CH2:19][CH2:20][CH2:21][C:9]1=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:23]N1C(C)(C)C(=O)N(Br)C1=O.O>CS(C)=O>[CH3:16][O:15][C:13]([C:11]1[C:10]2[C:17](=[O:22])[CH:18]([Br:23])[CH2:19][CH2:20][CH2:21][C:9]=2[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH:12]=1)=[O:14]

Participants

5

Reactant 3

HCID 962WaterHCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 60094089HCID 60094089, compound

Product 1

HCID 20872400HCID 20872400, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 4-Oxo-5,6,7,8-tetrahydro-4H-cyclohepta[b]pyrrole 1,3-dicarboxylic acid 3-methyl ester 1-tert-butyl ester(1.1 g, 3.6 mmol) in DMSO(20 mL) is added 1,3-dibromo-5,5-dimethylhydantoin(1.5 g, 5.4 mmol) portion wise with the aid of a cooling bath and the resulting mixture is stirred for 18 h at RT. Water is added and the reaction mixture is extracted with ether. The combined ether layers are washed with saturated brine, dried over Na2SO4, and concentrated in vacuo. The residue is purified by flash chromatography on silica gel (10% EtOAc/Hex to 25% EtOAc/Hex) to yield 915 mg of 5-Bromo-4-oxo-5,6,7,8-tetrahydro-4H-cyclohepta[b]pyrrole-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester as a bright yellow oil (66%). 1H NMR (CDCl3) 1.59 (s, 9H), 1.72-1.84 (m, 1H), 2.12-2.25 (m, 2H), 2.43-2.58 (m, 1H), 3.05-3.14 (m, 1H), 3.40-3.49 (m, 1H), 3.80 (s, 3H), 4.75 (m, 1H), 7.79 (s, 1H) Step 2: A mixture of 5-Bromo-4-oxo-5,6,7,8-tetrahydro-4H-cyclohepta[b]pyrrole-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester(467 mg, 1.2 mmol), 4-Amidinopyridine hydrochloride(953 mg, 6.1 mmol), and NaHCO3(813 mg, 9.7 mmol) in dioxane(20 mL) is refluxed for 20 h. After cooling to RT, MeOH(5 mL) is added and the mixture is filtered. The filtrate is concentrated in vacuo and the brown residue is purified by flash chromatography on silica gel (10% MeOH/CH2Cl2) to yield 197 mg of 2-Pyridin-4-yl-4,5,6,7-tetrahydro-3H-1,3,7-triaza-cyclopenta[e]azulene-9-carboxylic acid methyl ester as a yellow solid (53%). 1H NMR (CDCl3) 2.06 (quint, 2H), 2.98 (t, 2H), 3.04 (t, 2H), 3.91 (s, 1H), 7.46 (s, 1H), 7.76 (d, 2H), 8.28 (br s, 1H)8.56 (d, 2H)

Workup

  1. extractionthe reaction mixture is extracted with ether
  2. washThe combined ether layers are washed with saturated brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by flash chromatography on silica gel (10% EtOAc/Hex to 25% EtOAc/Hex)

Sources & evidence

ORD record
ord-f1535a829cf64314bf7d2e5bad71fe44
Source dataset
uspto-grants-2005_09
Patent number
US06949562B2

Reaction notes

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