N-Methyloxindole → (1R,2S)-2-(1-benzyl-1H-indazol-6-yl)-1'-methylspiro[cyclopropane-1,3'-indolin]-2'-one

HRID 447503Notes

Reaction equation

HRID 447503 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C@:10]2([CH2:18][C@H:17]2[C:19]2[CH:27]=[C:26]3[C:22]([CH:23]=[N:24][N:25]3[CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:21][CH:20]=2)[C:9]1=[O:35])C1C=CC=CC=1.CS(O[C@@H](C1C=C2C(C=NN2CC2C=CC=CC=2)=CC=1)COS(C)(=O)=O)(=O)=O.CN1C2C(=CC=CC=2)CC1=O>>[CH2:28]([N:25]1[C:26]2[C:22](=[CH:21][CH:20]=[C:19]([C@H:17]3[C@@:10]4([C:11]5[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=5)[N:8]([CH3:1])[C:9]4=[O:35])[CH2:18]3)[CH:27]=2)[CH:23]=[N:24]1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

4

Reactant 3

HCID 6096N-MethyloxindoleHCID 58486358(1R,2S)-1'-benzyl-2-(1-benzyl-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-oneHCID 58486366(S)-1-(1-benzyl-1H-indazol-6-yl)ethane-1,2-diyl dimethanesulfonate

Product 1

HCID 58486234(1R,2S)-2-(1-benzyl-1H-indazol-6-yl)-1'-methylspiro[cyclopropane-1,3'-indolin]-2'-oneYield 84%

Procedure

The title compound was prepared in a manner similar to the method of (1R,2S)-1′-benzyl-2-(1-benzyl-1H-indazol-6-yl)spiro[cyclopropane-1,3′-indolin]-2′-one using (S)-1-(1-benzyl-1H-indazol-6-yl)ethane-1,2-diyl dimethanesulfonate (6.70 g, 15.8 mmol) and 1-methylindolin-2-one (2.33 g, 15.8 mmol). Purification via column chromatography (silica gel, 25-50% EtOAc in hexane) yielded the title compound as a pale-orange crystalline solid (5.01 g, 84%); 1H NMR (400 MHz, CDCl3) δ 8.00 (s, 1H), 7.60 (d, J=8.3 Hz, 1H), 7.30-7.25 (m, 3H), 7.18 (s, 1H), 7.13-7.10 (m, 3H), 6.92 (d, J=8.6 Hz, 1H), 6.85 (d, J=7.6 Hz, 1H), 6.55 (t, J=7.0 Hz, 1H), 5.76 (d, J=7.2 Hz, 1H), 5.63-5.49 (m, 2H), 3.41 (t, J=8.8 Hz, 1H), 3.33 (s, 3H), 2.22-2.18 (m, 1H), 2.00-1.96 (m, 1H); MS ESI 380.2 [M+H]+, calcd for [C25H21N3O+H]+ 380.18.

Workup

  1. customPurification via column chromatography (silica gel, 25-50% EtOAc in hexane)

Sources & evidence

ORD record
ord-e864e0eb789b4da3902e9d9347e28aff
Source dataset
uspto-grants-2013_07
Patent number
US08481525B2

Reaction notes

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