Ethyl Acetate → (S)-tert-butyl 3-(4-chloro-3-iodo-1H-pyrrolo[3,2-c]pyridin-1-yl)pyrrolidine-1-carboxylate

HRID 516185Notes

Reaction equation

[Cl:1][C:2]1[C:7]2[C:8]([I:11])=[CH:9][NH:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[H-].[Na+].CS(O[C@@H:19]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20]1)(=O)=O.C(OCC)(=O)C>CN(C=O)C.O>[Cl:1][C:2]1[C:7]2[C:8]([I:11])=[CH:9][N:10]([C@H:23]3[CH2:19][CH2:20][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:22]3)[C:6]=2[CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

The 4-chloro-3-iodo-1H-pyrrolo[3,2-c]pyridine (225 mg) obtained in Step 1 was dissolved in DMF (3.0 ml). After cooling to 0° C., 60% sodium hydride (64.5 mg) was added thereto. The (R)-tert-butyl 3-(methylsulfonyloxy)pyrrolidine-1-carboxylate (322 mg) obtained in Example 2 (Step 1) was added to the reaction mixture using DMF (2.0 ml), and the mixture was stirred overnight. 60% Sodium hydride (64.5 mg) was additionally added, and the mixture was stirred at 85° C. overnight. Ethyl acetate and water were added to the reaction mixture to separate the organic layer. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate) to obtain the title compound as a crude product (192 mg). Physical properties: m/z [M+H]+ 448.3

Workup

stirringthe mixture was stirred at 85° C. overnight
customto separate the organic layer
dry with materialThe organic layer was dried over anhydrous magnesium sulfate
distillationthe solvent was distilled off under reduced pressure
customThe resulting residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate)

Sources & evidence

ORD record: ord-ee0dba3db8474a4fb2dd2dd10b9873b1
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09108973B2

Reaction notes

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