Water → (1S,2R)-2-(4-chlorophenyl)-1'-(pyridin-4-ylmethyl)spiro[cyclopropane-1,3'-indolin]-2'-one

HRID 1805329Notes

Reaction equation

HRID 1805329 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[C@:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[NH:12][C:11]3=[O:19])[CH2:9]2)=[CH:4][CH:3]=1.Br[CH2:21][C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]2[C@:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([CH2:21][C:22]4[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=4)[C:11]3=[O:19])[CH2:9]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 6427994-(Bromomethyl)pyridineHCID 58305285(1S,2R)-2-(4-chlorophenyl)spiro[cyclopropane-1,3'-indolin]-2'-one

Product 1

HCID 58305312(1S,2R)-2-(4-chlorophenyl)-1'-(pyridin-4-ylmethyl)spiro[cyclopropane-1,3'-indolin]-2'-oneYield 77.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(1R,2S) and (1S,2R)-2-(4-chlorophenyl)spiro[cyclopropane-1,3′-indolin]-2′-one (135 mg, 0.5 mmol), 4-bromomethyl-pyridine (98 mg, 0.6 mmol) and Cs2CO3 (245 mg, 0.75 mmol) were dissolved in DMF (2 mL). The mixture was stirred at room temperature for 14 hours. The mixture was poured into water, extracted with ethyl acetate, dried and concentrated under reduced pressure. The residue was dissolved in 2 mL of DMF. Purification by preparative HPLC gave the title compound as little yellow solid (140 mg, 76%). LC/MS m/e calcd. for C22H17ClN2O: 360, observed (M+H)+: 361.2 1HNMR (400 MHz, MeOD-d4) δppm 2.22-2.37 (m, 2 H) 3.32-3.40 (m, 1 H) 5.39 (s, 2 H) 6.15 (d, J=7.58 Hz, 1 H) 6.74-6.85 (m, 1 H) 6.92 (d, J=7.83 Hz, 1 H) 7.10-7.19 (m, 1 H) 7.24-7.42 (m, 4 H) 7.93 (d, J=6.32 Hz, 2 H) 8.80 (d, J=6.06 Hz, 2 H). MS calcd. for C22H17ClN2O 360, obsd. (ESI+) [(M+H)+] 361.1.

Workup

  1. extractionextracted with ethyl acetate
  2. customdried
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in 2 mL of DMF
  5. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-498783e22a974b2984d08d5fbe8d10ce
Source dataset
uspto-grants-2013_01
Patent number
US08354443B2

Reaction notes

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