Diethylene Glycol Monomethyl Ether → HCID 131727235, compound

HRID 2377089Notes

Reaction equation

HRID 2377089 reaction equation
Cl[CH2:2][C:3]1[C:11]2[C:6](=[CH:7][N:8]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=2)[N:5]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[F:24])[CH:4]=1.[CH3:25][O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][OH:32].CCN(C(C)C)C(C)C>CN(C=O)C>[F:24][C:18]1[CH:19]=[C:20]([F:23])[CH:21]=[CH:22][C:17]=1[CH2:16][N:5]1[C:6]2=[CH:7][N:8]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=[C:11]2[C:3]([CH2:2][O:32][CH2:31][CH2:30][O:29][CH2:28][CH2:27][O:26][CH3:25])=[CH:4]1.[CH3:25][O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][OH:32]

Participants

5

Reactant 3

HCID 8134Diethylene Glycol Monomethyl EtherHCID 81531DiisopropylethylamineHCID 59855821HCID 59855821, compound

Product 1

HCID 131727235HCID 131727235, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of methyl 3-(chloromethyl)-1-(2,4-difluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (4 mL, 0.197M in CH2Cl2, 0.788 mmol)) [prepared as described in step 2 of example 40] in anhydrous DMF (10 mL) was added 2-(methoxyethoxy)-ethanol (0.47 g, 3.94 mmol, 0.43 mL, 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 and eluted with CH2Cl2-EtOAc 70:30 v/v, 0.4 L, CH2Cl2-EtOAc-MeOH 80:18:2 1.0 L, and CH2Cl2-EtOAc-MeOH 80:17.5:2.5 1.0 L, 25 mL fractions) using the flash technique. Fractions 42-80 were combined to afford 0.339 g (78%) of methyl 1-(2,4-difluorobenzyl)-3-{[2-(2-methoxyethoxy)ethoxy]methyl}-1H-pyrrolo[2,3-c]pyridine-5-carboxylate: 2-(methoxyethoxy)-ethanol (1:1) as a clear, colorless, viscous oil.

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 and eluted with CH2Cl2-EtOAc 70:30 v/v, 0.4 L, CH2Cl2-EtOAc-MeOH 80:18:2 1.0 L, and CH2Cl2-EtOAc-MeOH 80:17.5:2.5 1.0 L, 25 mL fractions)

Sources & evidence

ORD record
ord-7e97f347cf094ab390f660d11113b6bc
Source dataset
uspto-grants-2008_12
Patent number
US07468375B2

Reaction notes

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