Dichloromethane → 2-(3-(4-fluorobenzyl)-2-oxopyrrolidin-1-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

HRID 883171Notes

Reaction equation

HRID 883171 reaction equation
[F:1][C:2]1[CH:14]=[CH:13][C:5]([CH2:6][CH:7]2[CH2:11][CH2:10][NH:9][C:8]2=[O:12])=[CH:4][CH:3]=1.Br[C:16]1[S:17][C:18]([C:22]([NH:24][CH2:25][C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)=[O:23])=[C:19]([CH3:21])[N:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:14]=[CH:13][C:5]([CH2:6][CH:7]2[CH2:11][CH2:10][N:9]([C:16]3[S:17][C:18]([C:22]([NH:24][CH2:25][C:26]4[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=4)=[O:23])=[C:19]([CH3:21])[N:20]=3)[C:8]2=[O:12])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 10149056HCID 10149056, compoundHCID 666315502-Bromo-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

Product 1

HCID 248018402-(3-(4-fluorobenzyl)-2-oxopyrrolidin-1-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamideYield 33.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 3-(4-fluorobenzyl)pyrrolidin-2-one (0.074 g, 0.39 mmol), 2-bromo-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide (0.10 g, 0.32 mmol), cesium carbonate (0.16 g, 0.48 mmol), [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) complex with dichloromethane (1:1) (0.005 g, 0.006 mmol) and xantphos (0.007 g, 0.013 mmol) in anhydrous toluene (2 mL) was subjected to microwave irradiation at 80° C. for 35 min. The reaction mixture was concentrated in vacuo and the residue was purified by column chromatography (ethyl acetate/hexanes (3/1)) to afford the title compound as a white solid (0.045 g, 33%): mp 169-170° C. (hexanes/ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 8.59 (s, 1H), 8.52 (d, J=4.5 Hz, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.30-7.23 (m, 1H), 7.14 (dd, J=8.0, 5.5 Hz, 2H), 6.95 (t, J=8.8 Hz, 2H), 6.16 (t, J=5.6 Hz, 1H), 4.59 (d, J=5.6 Hz, 2H), 4.07-3.95 (m, 1H), 3.92-3.79 (m, 1H), 3.20 (dd, J=13.9, 4.5 Hz, 1H), 3.07-2.93 (m, 1H), 2.83-2.74 (m, 1H), 2.61 (s, 3H), 2.32-2.18 (m, 1H), 1.98-1.82 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 174.8, 163.4, 162.5, 155.5, 153.2, 149.3, 149.1, 135.7, 133.8, 133.7, 130.4, 123.7, 118.2, 115.6, 45.9, 44.4, 41.5, 35.6, 24.2, 17.3; MS (ES+) m/z 425.3 (M+1).

Workup

  1. customirradiation at 80° C. for 35 min
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe residue was purified by column chromatography (ethyl acetate/hexanes (3/1))

Sources & evidence

ORD record
ord-94eab04301e24683bf0e034e42849482
Source dataset
uspto-grants-2012_08
Patent number
US08236835B2

Reaction notes

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