Formaldehyde → HCID 52917807, compound

HRID 860878Notes

Reaction equation

HRID 860878 reaction equation
Cl.[CH3:2][C@@H:3]1[CH2:7][CH2:6][CH2:5][NH:4]1.[CH2:8]=O.[CH3:10][C:11]1[CH:12]=[N:13][C:14]2[C:19]([N:20]=1)=[CH:18][C:17]([C:21]1[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=1)=[CH:16][CH:15]=2>CCO>[CH3:2][C@@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[CH2:8][CH2:10][C:11]1[CH:12]=[N:13][C:14]2[C:19]([N:20]=1)=[CH:18][C:17]([C:21]1[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=1)=[CH:16][CH:15]=2

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 11147704(2R)-(-)-2-Methylpyrrolidine hydrochlorideHCID 671046614-(3-Methyl-6-quinoxalinyl)benzonitrile

Product 1

HCID 52917807HCID 52917807, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

(2R)-2-Methylpyrrolidine hydrochloride 5 (973 mg, 8.0 mmol) and 37% aqueous solution of formaldehyde (0.57 mL, 7.0 mmol) were combined in EtOH (20 mL) and heated in a sealed tube at 85° C. for 1 hour. The mixture was allowed to cool to room temperature, treated with the products from Example 61C (500 mg, 2.0 mmol), and heated at 85° C. overnight. The mixture was allowed to cool to room and concentrated to dryness under vacuum. The residue was partitioned between IPAc (50 mL) and 20% brine (40 mL). The organic layer was separated, dried with Na2SO4, filtered, and the filtrate was concentrated under vacuum. The residue was purified by silica gel column chromatography eluting with heptane:acetone:CH2Cl2:Et3N (60:40:3:1) to provide the title compounds. MS 343 (M+H)+; 1H NMR (400 MHz, CDCl3) δ 8.74 (s, 1H), 7.72 (s, 1H), 8.16 (m, 2H), 8.06 (m, 2H), 7.85 (m, 2H), 7.70 (m, 4H), 3.17 (m, 8H), 2.52 (m, 2H), 2.31 (m, 2H), 2.17 (m, 2H), 1.83 (m, 2H), 1.65 (m, 4H), 1.32 (m, 2H). 13C NMR (400 MHz, CDCl3) δ 156.63, 156.41, 146.45, 145.16, 143.73, 143.70, 141.75, 141.53, 140.81, 140.60, 139.89, 139.04, 132.38, 129.66, 129.36, 128.42, 127.68, 127.65, 127.55, 137.13, 126.86, 118.29, 111.48, 111.40, 59.87, 53.93, 52.89, 35.83, 32.90, 21.98, 19.25.

Workup

  1. temperatureto cool to room temperature
  2. temperatureheated at 85° C. overnight
  3. temperatureto cool to room
  4. concentrationconcentrated to dryness under vacuum
  5. customThe residue was partitioned between IPAc (50 mL) and 20% brine (40 mL)
  6. customThe organic layer was separated
  7. dry with materialdried with Na2SO4
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated under vacuum
  10. customThe residue was purified by silica gel column chromatography
  11. washeluting with heptane:acetone:CH2Cl2:Et3N (60:40:3:1)

Sources & evidence

ORD record
ord-a945e24468134b4b83f58660bf8f3553
Source dataset
uspto-grants-2006_12
Patent number
US07153889B2

Reaction notes

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