Biphenyl-3-ylcarbamic acid phenyl ester → (S)-4-[4-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-butyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid biphenyl-3-ylamide

HRID 655585Notes

Reaction equation

HRID 655585 reaction equation
[OH:1][C@@H:2]1[CH2:9][N:8]([CH2:10][CH2:11][CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][NH:17][C@@H:16]([CH3:20])[C:15]2=[O:21])[CH2:7][CH2:6][C:3]21[CH2:5][CH2:4]2.C1([O:28][C:29](=O)[NH:30][C:31]2[CH:32]=[C:33]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:34]=[CH:35][CH:36]=2)C=CC=CC=1>C(#N)C>[C:33]1([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH:34]=[CH:35][CH:36]=[C:31]([NH:30][C:29]([N:17]2[CH2:18][CH2:19][N:14]([CH2:13][CH2:12][CH2:11][CH2:10][N:8]3[CH2:7][CH2:6][C:3]4([CH2:4][CH2:5]4)[C@H:2]([OH:1])[CH2:9]3)[C:15](=[O:21])[C@@H:16]2[CH3:20])=[O:28])[CH:32]=1

Participants

4

Reactant 2

HCID 18004898Biphenyl-3-ylcarbamic acid phenyl esterHCID 67079851(S)-1-[4-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-butyl]-3-methyl-piperazin-2-one2×

Product 1

HCID 59149890(S)-4-[4-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-butyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid biphenyl-3-ylamideYield 83%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of (S)-1-[4-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-butyl]-3-methyl-piperazin-2-one (intermediate 27; 50 mg, 0.17 mmol) and biphenyl-3-ylcarbamic acid phenyl ester (PCT Int. Appl. WO20050443810; 49 mg, 0.17 mmol) in acetonitrile (1 mL) was stirred at room temperature for 72 h, then concentrated under vacuum. Chromatography (SiO2; dichloro-methane/methanol/25% aq. ammonia solution 90:10:0.25) furnished the title compound (69 mg, 83%). White foam, MS (ISP)=491.3 (M+H)+.

Workup

  1. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-bc0fe7b47dff4793bddc26dcd3d1d787
Source dataset
uspto-grants-2011_12
Patent number
US08071586B2

Reaction notes

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