Dimethylformamide → 1h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(2,4-difluorophenyl)methyl]-3-[(2-methoxyethoxy)methyl]-,methyl ester

HRID 2377088Notes

Reaction equation

HRID 2377088 reaction equation
[F:1][C:2]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14]([O:16][CH3:17])=[O:15])[CH:13]=[C:8]2[C:7]([CH2:18]SC2C=CC=CC=2)=[CH:6]1.[CH3:31][O:32][CH:33](O)[CH3:34].CCN(C(C)C)C(C)C.CN(C=[O:49])C>>[F:1][C:2]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14]([O:16][CH3:17])=[O:15])[CH:13]=[C:8]2[C:7]([CH2:18][O:49][CH2:34][CH2:33][O:32][CH3:31])=[CH:6]1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 30156371-MethoxyethanolHCID 691988651h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(2,4-difluorophenyl)methyl]-3-[(phenylthio)methyl]-,methyl ester

Product 1

HCID 598558301h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(2,4-difluorophenyl)methyl]-3-[(2-methoxyethoxy)methyl]-,methyl esterYield 77%

Conditions

Temperature
40 °C

Procedure

To a solution of methyl 3-(chloromethyl)-1-(2,4-difluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (3 mL, 0.197M in CH2Cl2, 0.591 mmol) [prepared as described in step 2 of example 40] in anhydrous DMF (5 mL) was added methoxyethanol (0.25 g, 3.29 mmol, 0.26 mL, 5.5 eq.) followed by i-Pr2NEt (0.407 g, 3.14 mmol, 0.55 mL, 4 eq.). The mixture, under nitrogen, was placed in an oil bath and the bath was warmed to 40° C. After stirring for 24 hours (40° C.) the reaction was judged to by complete by HPLC-MS analysis and the volatiles were removed in vacuo (ca. 2 torr) to give a golden yellow oil. The crude material was purified by chromatography on a column of silica gel (40 mm OD, 100 g, 230-400 mesh, packed with CH2Cl2, eluted with CH2Cl2-EtOAc 70:30 v/v, 1.0 L, and CH2Cl2-EtOAc-MeOH 68:30:2, 1.0 L, 25 mL fractions) using the flash technique. Fractions 55-64 were combined to afford 0.148 g (77%) of methyl 1-(2,4-difluorobenzyl)-3-[(2-methoxyethoxy)methyl]-1H-pyrrolo[2,3-c]pyridine-5-carboxylate as a white, crystalline solid.

Workup

  1. customThe mixture, under nitrogen, was placed in an oil bath
  2. customthe volatiles were removed in vacuo (ca. 2 torr)
  3. customto give a golden yellow oil
  4. customThe crude material was purified by chromatography on a column of silica gel (40 mm OD, 100 g, 230-400 mesh, packed with CH2Cl2, eluted with CH2Cl2-EtOAc 70:30 v/v, 1.0 L, and CH2Cl2-EtOAc-MeOH 68:30:2, 1.0 L, 25 mL fractions)

Sources & evidence

ORD record
ord-b5ede65bd43c47c4bdf9c1e1a30e50b0
Source dataset
uspto-grants-2008_12
Patent number
US07468375B2

Reaction notes

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