N-Methyloxindole → (1R,2S)-2(1-(4-methoxybenzyl)-1H-indazol-6-yl)-1'-methylspiro[cyclopropane-1,3'-indolin]-2'-one

HRID 1410355Notes

Reaction equation

HRID 1410355 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:40][C@@H:41](C1C=C2C(C=NN2CC2C=CC(OC)=CC=2)=CC=1)COS(C)(=O)=O)(=O)=O.CN1C2C(=CC=CC=2)CC1=O>>[CH3:41][O:40][C:32]1[CH:31]=[CH:30][C:29]([CH2:28][N:25]2[C:26]3[C:22](=[CH:21][CH:20]=[C:19]([C@H:17]4[C@@:10]5([C:11]6[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=6)[N:8]([CH3:1])[C:9]5=[O:35])[CH2:18]4)[CH:27]=3)[CH:23]=[N:24]2)=[CH:34][CH:33]=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 86681513(S)-1-(1-(4-Methoxybenzyl)-1H-indazol-6-yl)ethane-1,2-diyl dimethanesulfonate

Product 1

HCID 68229467(1R,2S)-2(1-(4-methoxybenzyl)-1H-indazol-6-yl)-1'-methylspiro[cyclopropane-1,3'-indolin]-2'-oneYield 80%

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-(4-methoxybenzyl)-1H-indazol-6-yl)ethane-1,2-diyl dimethanesulfonate (2.03 g, 4.47 mmol) and 1-methylindolin-2-one (658 mg, 4.47 mmol). Purification using Biotage Isolera (silica gel, 20-50% EtOAc in hexane) yielded the title compound as a yellowish crystalline solid (1.47 g, 80%); 1H NMR (400 MHz, CD3OD) δ 7.98 (s, 1H), 7.61 (d, J=8.4 Hz, 1H), 7.43 (s, 1H), 7.13-7.06 (m, 3H), 6.97 (d, J=7.8 Hz, 1H), 6.92 (d, J=8.4 Hz, 1H), 6.80 (d, J=8.3 Hz, 2H), 6.50 (t, J=7.6 Hz, 1H), 5.78 (d, J=7.6 Hz, 1H), 5.58-5.47 (m, 2H), 3.72 (s, 3H), 3.36-3.30 (m, 4H), 2.22-2.19 (m, 1H), 2.16-2.12 (m, 1H); MS ESI 410.2 [M+H]+, calcd for [C26H23N3O2+H]+ 410.19.

Workup

  1. customPurification

Sources & evidence

ORD record
ord-1b861c6feedb49e3bafb6d98bd6ccc46
Source dataset
uspto-grants-2014_12
Patent number
US08921545B2

Reaction notes

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