Diisopropylethylamine → HCID 131727236, compound

HRID 2377090Notes

Reaction equation

HRID 2377090 reaction equation
ClC[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](CC2C=CC(F)=CC=2F)[CH:4]=1.[CH3:25][C:26]1([CH3:33])[O:30][C@H:29]([CH2:31][OH:32])[CH2:28][O:27]1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:25][C:26]1([CH3:33])[O:30][C@H:29]([CH2:31][O:32][CH2:15][O:14][C:12]([C:9]2[CH:10]=[C:11]3[CH:3]=[CH:4][NH:5][C:6]3=[CH:7][N:8]=2)=[O:13])[CH2:28][O:27]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 736056(R)-SolketalHCID 59855821HCID 59855821, compound

Product 1

HCID 131727236HCID 131727236, compound

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 (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 (R)-(−)-2,2-Dimethyl-1,3-dioxolane-4-methanol (0.37 ml, 2.955 mmol, 5.0 eq.) followed by i-Pr2NEt (0.4079, 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 50:50 v/v, 1.0 L, 25 mL fractions) using the flash technique. Fractions 30-54 were combined to afford 0.224 g (85%) of Methyl 1-(2,4-difluorobenzyl)-3-({([(4R)-2,2-dimethyl -1,3-dioxolan-4-yl]methoxy}methyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate as a colorless 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 with CH2Cl2, eluted with CH2Cl2-EtOAc 50:50 v/v, 1.0 L, 25 mL fractions)

Sources & evidence

ORD record
ord-e0ca07b9a12842438b21e459ae615d53
Source dataset
uspto-grants-2008_12
Patent number
US07468375B2

Reaction notes

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