HCID 86698155, compound → HCID 86698154, compound

HRID 632872Notes

Reaction equation

HRID 632872 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[N:8]=[C:9]([CH2:17][N:18]3[C:22]4[CH:23]=[N:24][CH:25]=[CH:26][C:21]=4[N:20]([CH:27]4[CH2:29][CH2:28]4)[C:19]3=[O:30])[N:10]([CH2:11][CH2:12][CH2:13][C:14](=[O:16])[CH3:15])[C:5]2=[CH:4][CH:3]=1.[Li][CH3:32]>C1COCC1.O>[Cl:1][C:2]1[N:7]=[C:6]2[N:8]=[C:9]([CH2:17][N:18]3[C:22]4[CH:23]=[N:24][CH:25]=[CH:26][C:21]=4[N:20]([CH:27]4[CH2:29][CH2:28]4)[C:19]3=[O:30])[N:10]([CH2:11][CH2:12][CH2:13][C:14]([OH:16])([CH3:32])[CH3:15])[C:5]2=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 86698155HCID 86698155, compoundHCID 178418348HCID 178418348, compound

Product 1

HCID 86698154HCID 86698154, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ketone 75-1 (210 mg, 0.497 mmole) in THF was added MeLi (0.466 mL, 1.5 eq, 1.6 M in THF) dropwise, at 0° C. The resulting mixture was stirred at RT overnight, then was heated at 50° C. for 2 hours. After cooling to RT, the reaction mixture was poured in water, extracted with dichloromethane, dried over MgSO4 and concentrated. The residue was purified by column chromatography using dichloromethane and methanol, followed by a purification by prep HPLC on RP SunFire Prep C18 OBD-10 μm,30×150 mm, and mobile phase (0.25% NH4HCO3 solution in water, CH3CN) to give 11 mg of the desired compound 75. LCMS m/z=441 (M+H)+; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.97-1.05 (m, 2 H), 1.11-1.22 (m, 2 H), 1.17 (s, 6 H), 1.43-1.53 (m, 2 H), 1.74 (br. s., 1 H), 1.79-1.91 (m, 2 H), 2.82-3.05 (m, 1 H), 4.40 (t, J=7.5 Hz, 2 H), 5.39 (s, 2 H), 7.11 (d, J=5.0 Hz, 1 H), 7.20 (d, J=8.3 Hz, 1 H), 7.64 (d, J=8.3 Hz, 1 H), 8.31 (d, J=5.0 Hz, 1 H), 8.70 (s, 1 H).

Workup

  1. customat 0° C
  2. temperaturewas heated at 50° C. for 2 hours
  3. temperatureAfter cooling to RT
  4. extractionextracted with dichloromethane
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography
  8. customfollowed by a purification by prep HPLC on RP SunFire Prep C18 OBD-10 μm,30×150 mm, and mobile phase (0.25% NH4HCO3 solution in water, CH3CN)

Sources & evidence

ORD record
ord-9a06c3f146cc485c86664e371aa4bd5e
Source dataset
uspto-grants-2016_04
Patent number
US09321767B2

Reaction notes

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