Cyclobutanone → HCID 50940101, compound

HRID 2089063Notes

Reaction equation

HRID 2089063 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10](S(C3C=CC=CC=3)(=O)=[O:18])[CH:9]=2)[N:5]=[C:4]([NH:26][CH:27]2[CH2:32][CH2:31][CH2:30][CH:29]([NH2:33])[CH2:28]2)[N:3]=1.[C:34]1(=[O:38])[CH2:37][CH2:36][CH2:35]1.[BH3-]C#N.[Na+]>CO.O.[Cl-].[Zn+2].[Cl-]>[C:34]([O-:38])(=[O:18])[CH3:37].[NH4+:3].[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=2)[N:5]=[C:4]([NH:26][CH:27]2[CH2:32][CH2:31][CH2:30][CH:29]([NH:33][CH:34]3[CH2:37][CH2:36][CH2:35]3)[CH2:28]2)[N:3]=1

Participants

8

Reactant 3

HCID 14496CyclobutanoneHCID 5003444Sodium cyanoborohydrideHCID 87192197HCID 87192197, compound

Product 2

HCID 517165Ammonium AcetateHCID 50940101HCID 50940101, compoundYield 31.9%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of Example 270a (350 mg, crude, ˜0.414 mmol) in MeOH (5 mL) was added cyclobutanone (29.0 mg, 0.414 mmol) and the solution was stirred at room temperature for 10 minutes before NaCNBH3 (52.0 mg, 0.828 mmol) and zinc chloride (0.6 mg, 0.004 mmol) were added. The reaction mixture was stirred at room temperature overnight and concentrated in vacuo. To the residue was added dioxone (5 mL) and NaOH (20%, 1 mL) and stirred at 90° C. for 1 hour. The reaction mixture was concentrated and purified by reverse-phase HPLC performed on a Phenomenex Luna C8 AXIA column (30×75 mm, 100 Å) using a gradient of 10% to 95% acetonitrile: 10 mM ammonium acetate in water over 12 minutes at a flow rate of 50 mL/minutes to provide the title compound (26 mg, 0.066 mmol, 16% yield). MS (ESI) m/e 397 (M+H)+; 1H NMR (400 MHz, DMSO-d6) ppm 0.95-2.21 (m, 16H) 2.55-2.65 (m, 1H) 3.26-3.36 (m, 1H) 3.79-3.92 (m, 1H) 7.07 (s, 1H) 7.11 (d, J=7.63 Hz, 1H) 7.17 (dd, J=7.93, 4.58 Hz, 1H) 8.29 (dd, J=4.73, 1.68 Hz, 1H) 8.34 (s, 1H) 8.77 (d, J=7.63 Hz, 1H).

Workup

  1. additionwere added
  2. concentrationconcentrated in vacuo
  3. additionTo the residue was added dioxone (5 mL) and NaOH (20%, 1 mL)
  4. stirringstirred at 90° C. for 1 hour
  5. concentrationThe reaction mixture was concentrated
  6. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-96f796d2fad84d3da6cbe0fd9570838b
Source dataset
uspto-grants-2013_05
Patent number
US08435980B2

Reaction notes

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