Piperidine → Spiro(cyclopropane-1,3'-indolin)-2'-one

HRID 1805313Notes

Reaction equation

HRID 1805313 reaction equation
ClC1C=CC([C@@H:8]2[C@:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12](CC4C=C(C=CC=4)C(O)=O)[C:11]3=[O:29])[CH2:9]2)=CC=1.ClC1C=CC([C@H]2[C@@]3(C4C(=CC=CC=4)N(CC4C=C(C=CC=4)C(O)=O)C3=O)C2)=CC=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.N1CCCCC1>CN(C=O)C>[NH:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]2([CH2:9][CH2:8]2)[C:11]1=[O:29]

Participants

7

Reactant 5

HCID 8082PiperidineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 532303493-(((1R,2S)-2-(4-chlorophenyl)-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)methyl)benzoic acidHCID 53244689HCID 53244689, compound

Product 1

HCID 12701643Spiro(cyclopropane-1,3'-indolin)-2'-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(((1S,2R)-2-(4-chlorophenyl)-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)methyl)benzoic acid and 3-(((1R,2S)-2-(4-chlorophenyl)-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)methyl)benzoic acid (prepared according to Scheme 1) (60 mg, 0.15 mmol), 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl) (44 mg, 0.225 mmol 1.5 mmol), anhydrous 1-Hydroxybenzotriazole (HOBt) (31 mg, 0.225 mmol) and piperidine (15 mg, 0.18 mmol) were dissolved in DMF. The mixture was stirred at room temperature for 14 hours. (1R,2S) and (1S,2R)-2-(4-chlorophenyl)-1′-(3-(piperidine-1-carbonyebenzyl)spiro[cyclopropane-1,3′-indolin]-2′-one were purified by preparative HPLC as a white solid (42 mg, 60%). LC/MS m/e calcd. for C29H27ClN2O2: 470, observed (M+H)+: 471.2 1H NMR (400 MHz, MeOD-d4) δppm 1.41 (br. s., 2 H) 1.67 (br. s., 4 H) 2.19-2.30 (m, 2 H) 3.28 (br.s., 2 H) 3.30 (s, 1 H) 3.69 (br. s., 2 H) 5.14 (s, 2 H) 6.11 (d, J=7.33 Hz, 1 H) 6.74 (t, J=7.20 Hz, 1 H) 6.91 (d, J=7.83 Hz, 1 H) 7.03-7.15 (m, 1 H) 7.20-7.28 (m, 2 H) 7.28-7.38 (m, 4 H) 7.43-7.57 (m, 2 H).

Workup

  1. custom(1R,2S) and (1S,2R)-2-(4-chlorophenyl)-1′-(3-(piperidine-1-carbonyebenzyl)spiro[cyclopropane-1,3′-indolin]-2′-one were purified by preparative HPLC as a white solid (42 mg, 60%)

Sources & evidence

ORD record
ord-0a21b5da31e543ee9804a7c935692025
Source dataset
uspto-grants-2013_01
Patent number
US08354443B2

Reaction notes

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