Sodium Iodide → 5-(2-chloro-4-cyanophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid methyl ester

HRID 76867Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:26])[CH:4]([C:17]1[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][C:18]=1[Cl:25])[N:5]1[C:9]([CH2:10][CH2:11]OS(C)(=O)=O)=[CH:8][N:7]=[CH:6]1.C([O-])([O-])=O.[K+].[K+].[Na+].[I-].CCN(CC)CC>CN(C=O)C>[CH3:1][O:2][C:3]([C:4]1([C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][C:18]=2[Cl:25])[N:5]2[CH:6]=[N:7][CH:8]=[C:9]2[CH2:10][CH2:11]1)=[O:26]

Participants

Conditions

Temperature: 80 °C

Procedure

The crude (2-chloro-4-cyanophenyl)-[5-(2-methanesulfonyloxyethyl)imidazol-1-yl]-acetic acid methyl ester (2.56 g, 6.45 mmol) is dissolved in dry DMF (50 mL) and to it is added K2CO3 (2.67 g, 19.4 mmol), NaI (2.9 g, 19.4 mmol) and Et3N (2.7 mL, 19.4 mmol). The reaction is stirred at 80° C. for 2 h before being concentrated to dryness. The residue is then diluted with EtOAc and washed with water. The organic layer is dried (Na2SO4) and evaporated to give a crude residue that is purified via flash column chromatography (Acetone/CH2Cl2 1:3) to give 5-(2-chloro-4-cyanophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid methyl ester as an oil. MS (ESI) m/z 302.2, 304.2 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm 2.64-2.76 (m, 2H), 2.97-3.06 (m, 1H), 3.84 (s, 3H), 3.86-3.93 (m, 1H), 6.56 (d, J=8.1 Hz, 1H), 6.87 (s, 1H), 7.50 (obs d, J=8.1 Hz, 1H), 7.52 (s, 1H), 7.73 (s, 1H).

Workup

concentrationbefore being concentrated to dryness
additionThe residue is then diluted with EtOAc
washwashed with water
dry with materialThe organic layer is dried (Na2SO4)
customevaporated
customto give a crude residue that
customis purified via flash column chromatography (Acetone/CH2Cl2 1:3)

Sources & evidence

ORD record: ord-54caaf070207408eabc26465ceb09ccb
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835646B2

Reaction notes

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