Potassium Carbonate → HCID 58748285, compound

HRID 1162654Notes

Reaction equation

Cl.[CH2:2]([O:4][C:5]([C@@H:7]1[C@@H:11]([C:12](=[O:28])[NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]3=[O:26])=[CH:16][C:15]=2[F:27])[CH2:10][NH:9][CH2:8]1)=[O:6])[CH3:3].C([O-])([O-])=O.[K+].[K+].Br[CH2:36][C:37]([NH:39][C:40]1[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][N:41]=1)=[O:38]>C(#N)C>[CH2:2]([O:4][C:5]([C@@H:7]1[C@@H:11]([C:12](=[O:28])[NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]3=[O:26])=[CH:16][C:15]=2[F:27])[CH2:10][N:9]([CH2:36][C:37](=[O:38])[NH:39][C:40]2[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][N:41]=2)[CH2:8]1)=[O:6])[CH3:3]

Participants

Conditions

Temperature: 25 °C

Procedure

(3R,4R)-4-[2-Fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-pyrrolidine-3-carboxylic acid ethyl ester hydrochloride (0.315 g; synthesis described in EP04101265.9 example 28 step 3) is suspended in acetonitrile (10 ml) and K2CO3 (0.425 g) is added as solid. 2-Bromo-N-(5-chloro-2-pyridinyl)-acetamide (0.23 g) is added and the reaction mixture is stirred at 25° C. for 18 h. After that the mixture is heated for 3 h to 80° C., cooled to 25° C. and filtered. The filtrate is evaporated to dryness followed by flash chromatography over silica gel using DCM/MeOH/NH3 as eluent to yield 0.203 g (46.3%) (3R,4R)-1-[(5-chloro-pyridin-2-ylcarbamoyl)-methyl]-4-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarba-moyl]-pyrrolidine-3-carboxylic acid ethyl ester. White solid. MS 542.3 [M+H+].

Workup

temperatureAfter that the mixture is heated for 3 h to 80° C.
temperaturecooled to 25° C.
filtrationfiltered
customThe filtrate is evaporated to dryness

Sources & evidence

ORD record: ord-d6531614c2854293a04ed1ad60aeb9e0
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07820699B2

Reaction notes

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