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Ethyl chloroformate → 1h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(4-fluorophenyl)methyl]-3-[[2-(2-oxo-1-pyrrolidinyl)ethoxy]methyl]-,methyl ester

HRID 2377109
Notes
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Reaction equation

HRID 2377109 reaction equation
CN([CH2:4][C:5]1[C:13]2[C:8](=[CH:9][N:10]=[C:11]([C:14]([O:16][CH3:17])=[O:15])[CH:12]=2)[N:7]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[CH:6]=1)C.ClC(OCC)=O.[OH:32][CH2:33][CH2:34][N:35]1[CH2:39][CH2:38][CH2:37][C:36]1=[O:40].C(N(C(C)C)C(C)C)C>C(Cl)Cl.CCOC(C)=O.CN(C=O)C>[F:25][C:22]1[CH:21]=[CH:20][C:19]([CH2:18][N:7]2[C:8]3=[CH:9][N:10]=[C:11]([C:14]([O:16][CH3:17])=[O:15])[CH:12]=[C:13]3[C:5]([CH2:4][O:32][CH2:33][CH2:34][N:35]3[CH2:39][CH2:38][CH2:37][C:36]3=[O:40])=[CH:6]2)=[CH:24][CH:23]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 10928Ethyl chloroformateHCID 769801-(2-Hydroxyethyl)-2-pyrrolidinoneHCID 81531DiisopropylethylamineHCID 59855831HCID 59855831, compound

Product 1

HCID 691986491h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(4-fluorophenyl)methyl]-3-[[2-(2-oxo-1-pyrrolidinyl)ethoxy]methyl]-,methyl esterYield 76%

Reagents, catalysts & solvents

3
HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirring solution of methyl 3-[(dimethylamino)methyl]-1-(4-fluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (1.04 g, 3.05 mmol) in DCM (16 mL) under nitrogen was added ethyl chloroformate (0.330 g, 3.05 mmol). The solution was stirred for 2 hours at room temperature. At this time, 1-(2-hydroxyethyl)pyrrolidin-2-one (1.57 g, 12.18 mmol), ethyl(diisopropyl)amine (1.97 g, 15.23 mmol), and DMF (16 mL) were added to the reaction and the reaction heated to 55° C. After stirring for 24 hours (55° C.) the reaction was judged to be complete by HPLC-MS analysis and the volatiles were removed in vacuo (ca. 2 torr) to give red oil. The crude material was diluted with EtOAc (40 mL) and washed with water (4×20 mL) and brine (20 mL). The organic phase was separated, dried (Na2SO4), and concentrated in vacuo to afford the target compound, which was purified by chromatography on a column of silica gel. Fractions were combined to afford 0.961 g (76% yield) of methyl 1-(4-fluorobenzyl)-3-{[2-(2-oxopyrrolidin-1-yl)ethoxy]methyl}-1H-pyrrolo[2,3-c]pyridine-5-carboxylate as an off white solid. 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 1.90-2.01 (m, 2H) 2.32 (t, J=8.10 Hz, 2H) 3.42-3.51 (m, 4H) 3.64 (t, J=5.27 Hz, 2H) 4.00 (s, 3H) 4.69 (s, 2H) 5.36 (s, 2H) 7.01 (t, J=8.57 Hz, 2H) 7.11-7.18 (m, 2H) 7.28 (s, 1H) 8.51 (s, 1H) 8.73 (s, 1H).

Workup

  1. temperaturethe reaction heated to 55° C
  2. stirringAfter stirring for 24 hours (55° C.) the reaction
  3. customthe volatiles were removed in vacuo (ca. 2 torr)
  4. customto give red oil
  5. washwashed with water (4×20 mL) and brine (20 mL)
  6. customThe organic phase was separated
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customto afford the target compound, which
  10. customwas purified by chromatography on a column of silica gel

Sources & evidence

ORD record
ord-e930daf3165f4dd6822f64e3464bcc72
Source dataset
uspto-grants-2008_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07468375B2

Reaction notes

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