2-Methoxyethanol → HCID 24740541, compound

HRID 1160630Notes

Reaction equation

HRID 1160630 reaction equation
[H-].[Na+].F[C:4]1[CH:5]=[CH:6][C:7]2[N+:12]([O-:13])=[N:11][C:10]([NH:14][CH2:15][CH2:16][N:17]([CH3:19])[CH3:18])=[N:9][C:8]=2[CH:20]=1.[CH3:21][O:22][CH2:23][CH2:24][OH:25]>C1COCC1>[CH3:21][O:22][CH2:23][CH2:24][O:25][C:4]1[CH:5]=[CH:6][C:7]2[N+:12]([O-:13])=[N:11][C:10]([NH:14][CH2:15][CH2:16][N:17]([CH3:19])[CH3:18])=[N:9][C:8]=2[CH:20]=1

Participants

5

Reactant 3

HCID 80192-Methoxyethanol2×HCID 24758Sodium hydride2×HCID 58949422HCID 58949422, compound

Product 1

HCID 24740541HCID 24740541, compoundYield 96.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

NaH (66 mg, 60% dispersion in oil, 1.7 mmol) was added to a stirred solution of fluoride 12 (261 mg, 1.0 mmol) and 2-methoxyethanol (0.12 mL, 1.6 mmol) in THF (10 mL) at 20° C. and the mixture stirred at reflux temperature for 2 h. More NaH (66 mg, 1.6 mmol) and 2-methoxyethanol (0.12 mL, 1.6 mmol) were added and the mixture stirred at reflux temperature for 16 h. The mixture was cooled to 20° C. and carefully quenched with water (5 mL). The solvent was evaporated and the residue partitioned between DCM (50 mL) and water (50 mL). The organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH/DCM, to give 1-oxide 13 (296 mg, 93%) as a yellow solid, mp (MeOH/EtOAc) 139-141° C.; 1H NMR δ 8.14 (d, J=9.4 Hz, 1 H, H-8), 6.91 (dd, J=9.4, 2.6 Hz, 1 H, H-7), 6.84 (d, J=2.6 Hz, 1 H, H-5), 5.91 (br s, 1 H, NH), 4.20-4.23 (m, 2 H, CH2O), 3.71-3.74 (m, 2 H, CH2O), 3.51-3.56 (m, 2 H, CH2N), 3.46 (s, 3 H, OCH3), 2.55 (br dd, J=6.0, 5.9 Hz, 2 H, CH2N), 2.28 [s, 6 H, (CH3)2]; 13C NMR δ 164.6, 159.6, 151.4, 126.1, 122.1, 118.0, 104.6, 70.5, 68.0, 59.3, 57.5, 45.1 (2), 38.7. Anal. Calcd for C14H21N5O3: C, 54.7; H, 6.9; N, 22.8. Found: C, 54.5; H, 6.7; N, 22.7%.

Workup

  1. temperatureat reflux temperature for 2 h
  2. stirringthe mixture stirred
  3. temperatureat reflux temperature for 16 h
  4. customcarefully quenched with water (5 mL)
  5. customThe solvent was evaporated
  6. customthe residue partitioned between DCM (50 mL) and water (50 mL)
  7. customThe organic fraction was dried
  8. customthe solvent evaporated
  9. customThe residue was purified by chromatography
  10. washeluting with a gradient (0-10%) of MeOH/DCM

Sources & evidence

ORD record
ord-5f0f8383e74b4471934bede0851f405b
Source dataset
uspto-grants-2010_10
Patent number
US07816521B2

Reaction notes

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