Potassium Carbonate → methyl 4-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

HRID 513174Notes

Reaction equation

HRID 513174 reaction equation
C(OC([NH:11]/[C:12](=[CH:17]\[C:18]1[C:19]([Cl:25])=[N:20][CH:21]=[CH:22][C:23]=1I)/[C:13]([O:15][CH3:16])=[O:14])=O)C1C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].N1CCC[C@H]1C(O)=O>O1CCOCC1.[Cu]I>[Cl:25][C:19]1[C:18]2[CH:17]=[C:12]([C:13]([O:15][CH3:16])=[O:14])[NH:11][C:23]=2[CH:22]=[CH:21][N:20]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 86720566Methyl (2Z)-2-{[(benzyloxy)carbonyl]amino}-3-(2-chloro-4-iodopyridin-3-yl)prop-2-enoate

Product 1

HCID 26599236methyl 4-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylateYield 90.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Procedure

Methyl (2Z)-2-{[(benzyloxy)carbonyl]amino}-3-(2-chloro-4-iodopyridin-3-yl)prop-2-enoate (11.46 g, 24.25 mmole), K2CO3 (10.05 g, 72.7 mmole), CuI (0.462 g, 2.425 mmole), and L-proline (0.558 g, 4.85 mmole) were combined in 1,4-dioxane (120 mL). The mixture was degassed (3× pump/N2) then heated to reflux. After stirring at reflux overnight the mixture was cooled to RT, diluted with saturated aqueous NH4Cl, and extracted with CH2Cl2 (3×). The combined organic layers were dried (MgSO4), filtered through a pad of Celite, and concentrated. The resulting solid was triturated with Et2O/hexanes to give the title compound (4.6 g, 90%) as an off-white solid. NMR (399 MHz, CDCl3): δ 9.25 (s, 1 H); 8.18 (d, J=5.8 Hz, 1 H); 7.35 (d, J=2.1 Hz, 1 H); 7.29 (d, J=5.9 Hz, 1 H); 3.99 (s, 3 H).

Workup

  1. customThe mixture was degassed (3× pump/N2)
  2. temperaturethen heated to reflux
  3. temperatureat reflux overnight the mixture
  4. additiondiluted with saturated aqueous NH4Cl
  5. extractionextracted with CH2Cl2 (3×)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. filtrationfiltered through a pad of Celite
  8. concentrationconcentrated
  9. customThe resulting solid was triturated with Et2O/hexanes

Sources & evidence

ORD record
ord-08a2be976f8c4a3b83cfba3466aedc17
Source dataset
uspto-grants-2015_08
Patent number
US09102673B2

Reaction notes

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