Acetonitrile--water (1/1) → HCID 178420857, compound

HRID 1441433Notes

Reaction equation

HRID 1441433 reaction equation
F[C:2](F)(F)C(O)=O.[N:8]12[CH2:15][CH2:14][CH:11]([CH2:12][CH2:13]1)[C@@H:10]([O:16][C:17]1[N:22]=[N:21][C:20]([C:23]3[CH:28]=[CH:27][C:26]([NH2:29])=[C:25]([N+:30]([O-])=O)[CH:24]=3)=[CH:19][CH:18]=1)[CH2:9]2.CC#N.O>CO.[OH-].[OH-].[Pd+2]>[NH:29]1[C:26]2[CH:27]=[CH:28][C:23]([C:20]3[N:21]=[N:22][C:17]([O:16][C@@H:10]4[CH:11]5[CH2:14][CH2:15][N:8]([CH2:13][CH2:12]5)[CH2:9]4)=[CH:18][CH:19]=3)=[CH:24][C:25]=2[N:30]=[CH:2]1

Participants

5

Reactant 2

HCID 18373917Acetonitrile--water (1/1)HCID 67070087HCID 67070087, compound

Product 1

HCID 178420857HCID 178420857, compound

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

The product of Example 29B (29 mg, 0.064 mmol) was dissolved in 2.0 mL of methanol and 6 mg of Pd(OH)2/C (Aldrich, 10 wt %) was added. The mixture was stirred under 50 psi of H2 for 30 min. The solution was filtered through a nylon membrane and concentrated. The residue was dissolved in DMF (0.25 mL) and treated with excess triethylorthoformate (0.1 mL). The solution was heated at 80° C. for 2 h, then cooled down to ambient temperature and stirred for 4 h. The title product was purified by preparative HPLC (Xterra™, column, Xterra RP-18 5 μm, 30×100 mm. Eluting Solvent, MeCN/H2O (NH4HCO3, 0.1 M, pH=10) (v. 40/60 to 70/30 over 20 min.) Flow rate, 75 mL/min., uv, 250 nm) as solid (13 mg, 0.04 mmol, 63%). 1H NMR (300 MHz, CD3OD) δ 1.57 (m, 1H), 1.73-1.94 (m, 2H), 2.08 (m, 1H), 2.34 (td, J=6.4, 3.6 Hz, 1H), 2.80-3.03 (m, 6H), 3.50 (ddd, J=14.5, 8.1, 1.5 Hz, 1H), 5.32 (m, 1H), 7.28 (d, J=9.2 Hz, 1H), 7.74 (d, J=8.5 Hz, 1H), 7.91 (d, J=8.5 Hz, 1H), 8.11 (d, J=9.2 Hz, 1H), 8.22 (s, 1H), 8.25 (s, 1H) ppm; MS (DCI/NH3): m/z 322 (M+H)+.

Workup

  1. filtrationThe solution was filtered through a nylon membrane
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in DMF (0.25 mL)
  4. additiontreated with excess triethylorthoformate (0.1 mL)
  5. temperaturecooled down to ambient temperature
  6. stirringstirred for 4 h

Sources & evidence

ORD record
ord-a60dbf9c132c406393793c739c3507f8
Source dataset
uspto-grants-2010_02
Patent number
US07655657B2

Reaction notes

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