Sodium hydride → Methyl 1-[2-(4-chlorophenoxy)ethyl]-4-(2-fluoropyridin-4-yl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

HRID 513193

Reaction equation

HRID 513193 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]2[C:13]3[CH:14]=[C:15]([C:17]([O:19][CH3:20])=[O:18])[NH:16][C:12]=3[CH:11]=[CH:10][N:9]=2)[CH:5]=[CH:4][N:3]=1.[H-].[Na+].Br[CH2:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=1>CN(C=O)C.O>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([O:26][CH2:25][CH2:24][N:16]2[C:12]3[CH:11]=[CH:10][N:9]=[C:8]([C:6]4[CH:5]=[CH:4][N:3]=[C:2]([F:1])[CH:7]=4)[C:13]=3[CH:14]=[C:15]2[C:17]([O:19][CH3:20])=[O:18])=[CH:28][CH:29]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 748541-(2-Bromoethoxy)-4-chlorobenzeneHCID 71212871methyl 4-(2-fluoropyridin-4-yl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

Product 1

HCID 71230366Methyl 1-[2-(4-chlorophenoxy)ethyl]-4-(2-fluoropyridin-4-yl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylateYield 82%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 4-(2-fluoropyridin-4-yl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylate (67 mg, 0.247 mmole) in DMF (1.2 mL) was added NaH (60% dispersion in mineral oil, 13 mg, 0.325 mmole) at RT. After gas evolution had ceased 1-(2-bromoethoxy)-4-chlorobenzene (76 mg, 0.321 mmole) was added and the mixture was heated to 60° C. After 3 hr the mixture was diluted with H2O and extracted with EtOAc (3×). The combined organic layers were washed with H2O and brine, dried (MgSO4), filtered, and concentrated. Flash column chromatography (Biotage-SNAP-10 g SiO2, 35% EtOAc/hexanes) gave the title compound (86 mg, 82%) as a white foam. 1H NMR (400 MHz, CDCl3): δ 8.58 (d, J=5.9 Hz, 1 H); 8.39 (d, J=5.2 Hz, 1 H); 7.79 (d, J=5.4 Hz, 1 H); 7.60-7.51 (m, 3 H); 7.18-7.15 (m, 2 H); 6.72-6.67 (m, 2 H); 5.02-4.96 (m, 2 H); 4.39-4.33 (m, 2 H); 3.97 (s, 3 H).

Workup

  1. additionwas added
  2. extractionextracted with EtOAc (3×)
  3. washThe combined organic layers were washed with H2O and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-c9857d6da2f44e5c953eb9c93a808675
Source dataset
uspto-grants-2015_08
Patent number
US09102673B2

Linked notes

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