Trimethylsilyldiazomethane → HCID 59315581, compound

HRID 1967642Notes

Reaction equation

HRID 1967642 reaction equation
[Si]([O:8][CH2:9][C@@H:10]([C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][C:13]=1[CH3:21])[CH3:11])(C(C)(C)C)(C)C.[NH2:22][C:23]1[CH:32]=[C:31]2[C:26]([CH:27]=[CH:28][NH:29][C:30]2=[O:33])=[CH:25][CH:24]=1.O.[C:35]([OH:39])(=[O:38])[CH:36]=O.[Si](C=[N+]=[N-])(C)(C)[CH3:41]>C(#N)C.CN(C=O)C>[OH:8][CH2:9][C@@H:10]([C:12]1[CH:17]=[CH:16][C:15]([CH:36]([NH:22][C:23]2[CH:32]=[C:31]3[C:26]([CH:27]=[CH:28][NH:29][C:30]3=[O:33])=[CH:25][CH:24]=2)[C:35]([O:39][CH3:41])=[O:38])=[CH:14][C:13]=1[CH3:21])[CH3:11]

Participants

7

Reactant 4

HCID 167693TrimethylsilyldiazomethaneHCID 155418167-Aminoisoquinolin-1(2H)-oneHCID 15620607Glyoxylic acid, monohydrateHCID 68590565HCID 68590565, compound

Product 1

HCID 59315581HCID 59315581, compoundYield 66.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

In a reaction vial, Intermediate 10 (1.256 g, 4.07 mmol), Intermediate 3 (0.653 g, 4.07 mmol), and glyoxylic acid monohydrate (0.375 g, 4.07 mmol) were dissolved in acetonitrile (20 mL) and DMF (5 mL). The mixture was heated in an oil bath at 80° C. for 2 h. Solvent was removed under reduced pressure, the residue was dissolved in MeOH (5 mL), and benzene (15 mL) was added. To this solution, TMS-Diazomethane (2 M in ether) (5.09 mL, 10.19 mmol) was added dropwise at rt. The mixture was stirred for 15 min at rt, then was evaporated. The residue was purified by flash chromatography: (120 g) 50-100% EtOAc/hex. Eluted at −100% EtOAc. Fractions were combined and concentrated under reduced pressure to give Intermediate 16 (1.026 g, 2.70 mmol, 66.2% yield) as a yellow powder. MS (ESI) m/z 381.3. 1H-NMR: (Jeol ECX-400) (400 MHz, CDCl3) δ ppm 1.22 (d, J=7.15 Hz, 3H) 1.53-1.64 (m, 1H) 2.34 (d, J=3.30 Hz, 3H) 3.17-3.28 (m, 1H) 3.64-3.69 (m, 1H) 3.76 (s, 3H) 5.21 (s, 2H) 6.42 (d, J=7.15 Hz, 1H) 6.86-6.92 (m, 1H) 7.03 (d, J=6.05 Hz, 1H) 7.20 (dd, J=7.97, 3.02 Hz, 1H) 7.29 (s, 1H) 7.31-7.39 (m, 2H) 7.43 (d, J=3.30 Hz, 1H).

Workup

  1. customSolvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in MeOH (5 mL)
  3. additionbenzene (15 mL) was added
  4. customwas evaporated
  5. customThe residue was purified by flash chromatography
  6. washEluted at −100% EtOAc
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-41ab34730f00491d9ada5a936699092f
Source dataset
uspto-grants-2013_04
Patent number
US08420830B2

Reaction notes

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