Lawesson's reagent → tert-butyl (2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}-3-thioxopropyl]pyrrolidine-1-carboxylate

HRID 74729Notes

Reaction equation

HRID 74729 reaction equation
[CH3:1][O:2][C@@H:3]([C@@H:22]1[CH2:26][CH2:25][CH2:24][N:23]1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@@H:4]([CH3:21])[C:5](=O)[NH:6][C@H:7]([C:15]1[S:16][CH:17]=[CH:18][N:19]=1)[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.COC1C=CC(P2(=S)SP(C3C=CC(OC)=CC=3)(=S)[S:43]2)=CC=1>C1(C)C=CC=CC=1>[CH3:1][O:2][C@@H:3]([C@@H:22]1[CH2:26][CH2:25][CH2:24][N:23]1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@@H:4]([CH3:21])[C:5]([NH:6][C@H:7]([C:15]1[S:16][CH:17]=[CH:18][N:19]=1)[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[S:43]

Participants

4

Reactant 2

HCID 87949Lawesson's reagentHCID 14753401tert-butyl (2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidine-1-carboxylate

Product 1

HCID 86685720tert-butyl (2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}-3-thioxopropyl]pyrrolidine-1-carboxylateYield 33.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of #16 (350 mg, 0.739 mmol, 1 eq.) and 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-dithione (Lawesson's reagent) (324 mg, 0.776 mmol, 1.05 eq.) in toluene (6 mL, 0.1 M) was warmed to 100° C. After 10 minutes, the mixture was cooled to room temperature. Insoluble material was removed by filtration and the filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography (Gradient: 12% to 80% ethyl acetate in heptane) and then by reverse phase chromatography (Method E2) to give #17 (120 mg, 33%); HPLC (Protocol J): m/z 490.2 [M+H+], retention time=10.069 minutes; [α]20D−110 (c 0.24, MeOH); 1H NMR (400 MHz, CD3OD), characteristic signals: δ 7.78 (d, J=3.3 Hz, 1H), 7.51 (d, J=3.3 Hz, 1H), 7.32-7.37 (m, 2H), 7.24-7.30 (m, 2H), 7.17-7.23 (m, 1H), 6.52-6.61 (br m, 1H), 3.62 (br dd, J=15, 4 Hz, 1H), 3.37 (s, 3H), 2.98-3.09 (br m, 1H), 2.53-2.64 (br m, 1H), 1.60-1.78 (m, 2H), 1.49 (s, 9H), 1.27 (d, J=6.5 Hz, 3H).

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. customInsoluble material was removed by filtration
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe residue was purified by silica gel chromatography (Gradient: 12% to 80% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-1b53667518db441dab2e342d4706e843
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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