Diisopropylethylamine → (S)-tert-butyl 3-(1-(2-(dimethylamino)ethyl)-2-neopentyl-1H-benzo[d]imidazol-5-ylthio)pyrrolidine-1-carboxylate

HRID 241665Notes

Reaction equation

HRID 241665 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:5]2[N:6]([CH2:14][CH2:15][N:16]([CH3:18])[CH3:17])[C:7]([CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[N:8][C:4]=2[CH:3]=1.[SH:21][C@H:22]1[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23]1.C(N(CC)C(C)C)(C)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[CH3:17][N:16]([CH3:18])[CH2:15][CH2:14][N:6]1[C:5]2[CH:19]=[CH:20][C:2]([S:21][C@H:22]3[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23]3)=[CH:3][C:4]=2[N:8]=[C:7]1[CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 585135832-(5-bromo-2-neopentyl-1H-benzo[d]imidazol-1-yl)-N,N-dimethylethanamineHCID 59032356tert-Butyl (3S)-3-sulfanylpyrrolidine-1-carboxylate

Product 1

HCID 58513600(S)-tert-butyl 3-(1-(2-(dimethylamino)ethyl)-2-neopentyl-1H-benzo[d]imidazol-5-ylthio)pyrrolidine-1-carboxylateYield 70%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2-(5-bromo-2-neopentyl-1H-benzo[d]imidazol-1-yl)-N,N-dimethylethanamine (prepared in STEP A of Example 1, 1.93 g, 5.69 mmol), (S)-tert-butyl 3-mercaptopyrrolidine-1-carboxylate (STEP C, 7.42 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (165 mg, 0.285 mmol), tris(dibenzylideneacetone)dipalladium(0) (130 mg, 0.142 mmol) and N,N-diisopropylethylamine (1.10 g, 8.54 mmol) in 1,4-dioxane (25 mL) was stirred at 130° C. for 18 h. The mixture was concentrated and the residue was purified by silica gel column chromatography (pre-treatment with triethylamine, hexane-ethyl acetate, gradient) to give the title compound (1.83 g, 70%) as a brown oil.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by silica gel column chromatography (pre-treatment with triethylamine, hexane-ethyl acetate, gradient)

Sources & evidence

ORD record
ord-520a3e5306334576a9b9906484689ad4
Source dataset
uspto-grants-2014_02
Patent number
US08653063B2

Reaction notes

Loading…