Sodium hydride → (1R*,2S*)-2-(1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-one

HRID 447358Notes

Reaction equation

HRID 447358 reaction equation
[I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[NH:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15](/[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:16]=2)[CH:11]=[N:10]1>CN(C=O)C>[NH:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([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:16]=2)[CH:11]=[N:10]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 178517060(3E)-3-(1H-indazol-6-ylmethylidene)-1H-indol-2-one

Product 1

HCID 58486367(1R*,2S*)-2-(1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-oneYield 28%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of trimethylsulfoxonium iodide (264 mg, 1.2 mmol) in anhydrous DMF (40 mL) was added sodium hydride (60% dispersion in oil) (140 mg, 3.48 mmol) at 0° C. The mixture was stirred for 15 min after which time (E)-3-((1H-indazol-6-yl)methylene)indolin-2-one (151 mg, 0.58 mmol) was added. The solution was stirred overnight at rt. The reaction was quenched with sat. NH4Cl solution (10 mL), extracted with EtOAc (4×50 mL), dried over MgSO4 and concentrated to dryness. The major diastereomer was isolated by silica gel chromatography (EtOAc/Hex 1:1) as a beige solid (44 mg, 28%). 1H NMR (400 MHz, d6-DMSO) δ 13.01 (s, 1H), 10.61 (d, 1H J=8.3 Hz), 8.01 (s, 1H), 7.63 (d, 1H, J=8.3 Hz), 7.44 (s, 1H), 6.99 (t, 1H, J=7.5 Hz), 6.92 (d, 1H, J=8.0 Hz), 6.84 (d, 1H, J=8.0 Hz), 6.51 (t, 1H, J=7.0 Hz), 5.98 (d, 1H, 8.0 Hz), 3.20-3.17 (m, 1H), 2.30-2.26 (m, 1H), 2.00-1.95 (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 (10 mL)
  3. extractionextracted with EtOAc (4×50 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-c1e306ebde5845b19f700dd6a4299bcc
Source dataset
uspto-grants-2013_07
Patent number
US08481533B2

Reaction notes

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