Methyl iodide → 7-chloro-2-[(R)-3-methoxypyrrolidine-1-carbonyl]thieno[3,2-b]pyridine

HRID 1825064Notes

Reaction equation

HRID 1825064 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([N:13]3[CH2:17][CH2:16][C@@H:15]([OH:18])[CH2:14]3)=[O:12])[S:10][C:3]=12.[H-].[Na+].I[CH3:22]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([N:13]3[CH2:17][CH2:16][C@@H:15]([O:18][CH3:22])[CH2:14]3)=[O:12])[S:10][C:3]=12

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 207677587-chloro-2-[(R)-3-hydroxypyrrolidine-1-carbonyl]thieno[3,2-b]pyridine

Product 1

HCID 207677657-chloro-2-[(R)-3-methoxypyrrolidine-1-carbonyl]thieno[3,2-b]pyridineYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 7-chloro-2-[(R)-3-hydroxypyrrolidine-1-carbonyl]thieno[3,2-b]pyridine 4a (1.86 g, 6.6 mmole) in THF (150 ml) was cooled to −10° prior to addition of NaH (920 mg, 23 mmole as a 60% by wt. mineral oil dispersion). The resultant mixture was stirred at 0° for 40 minutes. Iodomethane (4 ml, 9.12 g, 64 mmole) was then added to the reaction which was stirred for another 3 hours, gradually warming to room temperature. The crude reaction mixture was quenched with saturated NaHCO3 (150 ml), then extracted with EtOAc (2×100 ml). The combined organic extracts were dried over Na2SO4 and concentrated, in vacuo, to give 2.4 g of an amber paste, which was purified by silica gel chromatography. Elution with CH2Cl2: CH3OH (98:2) and evaporation of the appropriate fractions gave 1.64 g (84%) of a yellow solid. 1H NMR (DMSO-d6): δ 8.73 (1H, d, J=5.1 Hz), 8.15 (1H, s), 7.69 (1H, d, J=5.1 Hz), 4.11–3.83 (3H, m), 3.69–3.47 (2H, m), 3.27, 3.24 (3H, s), 2.18–1.93 (2H, m). Anal. Calcd. for C13H23N2O2SCl: C, 52.61; H, 4.42; N, 9.44; S, 10.80; Cl, 11.95. Found: C, 52.76; H, 4.47; N, 9.38; S, 10.84; Cl, 12.01.

Workup

  1. customThe crude reaction mixture
  2. customwas quenched with saturated NaHCO3 (150 ml)
  3. extractionextracted with EtOAc (2×100 ml)
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. concentrationconcentrated, in vacuo
  6. customto give 2.4 g of an amber paste, which
  7. customwas purified by silica gel chromatography
  8. washElution
  9. customwith CH2Cl2: CH3OH (98:2) and evaporation of the appropriate fractions

Sources & evidence

ORD record
ord-86082cd6bd10475aa67ad8511548916e
Source dataset
uspto-grants-2006_05
Patent number
US07045528B2

Reaction notes

Loading…