Sodium hydride → (1R*,2S*)-2-(1H-indazol-5-yl)spiro[cyclopropane-1,3'-indolin]-2'-one

HRID 447357Notes

Reaction equation

HRID 447357 reaction equation
[I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[NH:9]1[C:17]2[C:12](=[CH:13][C:14](/[CH:18]=[C:19]3/[C:20](=[O:28])[NH:21][C:22]4[C:27]/3=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:15][CH:16]=2)[CH:11]=[N:10]1>CN(C=O)C>[NH:9]1[C:17]2[C:12](=[CH:13][C:14]([C@H:18]3[C@@:19]4([C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[NH:21][C:20]4=[O:28])[CH2:2]3)=[CH:15][CH:16]=2)[CH:11]=[N:10]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 178517063HCID 178517063, compound

Product 1

HCID 68633794(1R*,2S*)-2-(1H-indazol-5-yl)spiro[cyclopropane-1,3'-indolin]-2'-oneYield 18.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of trimethylsulfoxonium iodide (33 mg, 0.15 mmol) in anhydrous DMF (1 mL) was added sodium hydride (60% dispersion in oil) (16 mg, 0.4 mmol) at 0° C. The mixture was stirred for 15 min after which time (E)-3-((1H-indazol-5-yl)methylene)indolin-2-one (26 mg, 0.1 mmol) was added. The solution was stirred overnight at rt. The reaction was quenched with sat. NH4Cl solution (2 mL), extracted with EtOAc (50 mL), dried over MgSO4 and concentrated to dryness. The title was compound isolated by preparative HPLC) as a white solid (5 mg, 18%). 1H NMR (400 MHz, d6-DMSO) δ 13.03 (s, 1H), 10.58 (d, 1H, J=8.3 Hz), 8.02 (s, 1H), 7.74 (s, 1H), 7.40 (d, 1H, J=8.9 Hz), 7.11 (d, 1H, J=8.6 Hz), 6.98 (t, 1H, J=7.7 Hz), 6.83 (d, 1H, J=7.6 Hz), 6.50 (t, 1H, J=7.3 Hz), 5.94 (d, 1H, 7.5 Hz), 3.17-3.13 (m, 1H), 2.27-2.23 (m, 1H), 1.98-1.95 (m, 1H); MS ESI 276.1 [M+H]+, calcd for [C17H13N3O+H]+ 276.3.

Workup

  1. additionwas added
  2. customThe reaction was quenched with sat. NH4Cl solution (2 mL)
  3. extractionextracted with EtOAc (50 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-9c852a88b2364a5c90aaa45ff9071788
Source dataset
uspto-grants-2013_07
Patent number
US08481533B2

Reaction notes

Loading…