tetrahydrofuran N,N-dimethylformamide → HCID 178442317, compound

HRID 717224Notes

Reaction equation

HRID 717224 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:21][CH3:22])=[C:6]([CH:20]=1)[C:7]([NH:9][C:10]1[S:11][C:12]([C:15]([CH3:19])([CH3:18])[C:16]#[CH:17])=[N:13][N:14]=1)=[O:8].[CH3:23][C:24](C)([O-:26])[CH3:25].[K+].CN(C)C=O.O1CC[CH2:36][CH2:35]1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:21][CH3:22])=[C:6]([CH:20]=1)[C:7](/[N:9]=[C:10]1\[S:11][C:12]([C:15]([CH3:18])([CH3:19])[C:16]#[CH:17])=[N:13][N:14]\1[CH2:23][C@H:24]1[CH2:25][CH2:36][CH2:35][O:26]1)=[O:8]

Participants

4

Reactant 3

HCID 21974620tetrahydrofuran N,N-dimethylformamideHCID 23665647Potassium tert-butoxideHCID 87439520HCID 87439520, compound

Product 1

HCID 178442317HCID 178442317, compoundYield 29%

Conditions

Temperature
80 °C

Procedure

To a solution of Example 6B (250 mg, 0.75 mmol) in N,N-dimethylformamide/tetrahydrofuran (1:4, 10 mL) was added a solution of potassium tert-butoxide (Aldrich, 125 mg, 1.1 mmol) and Example 1B (285 mg, 1.1 mmol). The reaction mixture was stirred at 80° C. for 16 h, cooled to room temperature, quenched with saturated aqueous NaHCO3 (10 mL). The aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-1% methanol in dichloromethane) to afford 90 mg (29%) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.65 (s, 6H), 1.69-1.81 (m, 1H), 1.80-1.92 (m, 2H), 1.92-2.05 (m, 1H), 3.57 (s, 1H), 3.59-3.72 (m, 1H), 3.72-3.79 (m, 1H), 3.81 (s, 3H), 4.21-4.31 (m, 1H), 4.31-4.43 (m, 1H), 4.44-4.58 (m, 1H), 7.15 (d, J=9.1 Hz, 1H), 7.52 (dd, J=8.9, 3.0 Hz, 1H), 7.77 (d, J=2.8 Hz, 1H); MS (ESI+) m/z 420 (M+H)+.

Workup

  1. temperaturecooled to room temperature
  2. customquenched with saturated aqueous NaHCO3 (10 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×10 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-65eb225bfa9f41c48bc4e2e7237ad84c
Source dataset
uspto-grants-2015_11
Patent number
US09193713B2

Reaction notes

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