Methanol → HCID 20605630, compound

HRID 497410Notes

Reaction equation

HRID 497410 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]2[C:21](=O)[CH:20](Br)[CH2:19][CH2:18][CH2:17][C:7]=2[N:8](C(OC(C)(C)C)=O)[CH:9]=1)=[O:4].Cl.[C:25]([C:28]1[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=1)(=[NH:27])[NH2:26].C([O-])(O)=O.[Na+].CO>O1CCOCC1>[CH3:1][O:2][C:3]([C:5]1[C:6]2[C:21]3[N:26]=[C:25]([C:28]4[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=4)[NH:27][C:20]=3[CH2:19][CH2:18][CH2:17][C:7]=2[NH:8][CH:9]=1)=[O:4]

Participants

6

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 2776844Pyridine-4-amidine hydrochlorideHCID 20872400HCID 20872400, compound

Product 1

HCID 20605630HCID 20605630, compoundYield 53.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

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. temperatureis refluxed for 20 h
  2. filtrationthe mixture is filtered
  3. concentrationThe filtrate is concentrated in vacuo
  4. customthe brown residue is purified by flash chromatography on silica gel (10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-869b194dc894442a807b632a8b3b7afc
Source dataset
uspto-grants-2005_09
Patent number
US06949562B2

Reaction notes

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