Diisopropylethylamine → {(R)-1-[(S)-2-Benzyl-4-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine-1-carbonyl]-2-hydroxy-2-methyl-propyl}-carbamic acid tert-butyl ester

HRID 1423146Notes

Reaction equation

HRID 1423146 reaction equation
[CH2:1]([C@@H:8]1[NH:13][CH2:12][CH2:11][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:37]([O:41][C:42]([NH:44][C@H:45]([C:49]([OH:52])([CH3:51])[CH3:50])[C:46](O)=[O:47])=[O:43])([CH3:40])([CH3:39])[CH3:38].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CN(C=O)C>[C:37]([O:41][C:42](=[O:43])[NH:44][C@@H:45]([C:46]([N:13]1[CH2:12][CH2:11][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:9][C@@H:8]1[CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:47])[C:49]([OH:52])([CH3:50])[CH3:51])([CH3:40])([CH3:38])[CH3:39]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11299247N-(tert-Butoxycarbonyl)-3-hydroxy-D-valineHCID 16725642(S)-3-Benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine

Product 1

HCID 67291777{(R)-1-[(S)-2-Benzyl-4-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine-1-carbonyl]-2-hydroxy-2-methyl-propyl}-carbamic acid tert-butyl esterYield 69%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-3-Benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine (92 mg, 0.25 mmol) in CH2Cl2 (1 mL) and DMF (500 μL) at 0-5° C. was treated with diisopropylethylamine (87 μL, 0.50 mmol), (R)-2-(tert-butoxycarbonylamino)-3-hydroxy-3-methylbutanoic acid (64 mg, 0.28 mmol), followed by HATU (105 mg, 0.28). The reaction mixture was allowed to warm to room temperature and stir for 3 h. After this time the reaction mixture was evaporated and the residue purified by silica gel flash chromatography with 30% then 40% EtOAc/hexanes as eluant to afford the intermediate {(R)-1-[(S)-2-Benzyl-4-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine-1-carbonyl]-2-hydroxy-2-methyl-propyl}-carbamic acid tert-butyl ester as an oil (100 mg, 69%). LC/MS (Method B) 4.36 min, [M+1]+ 582.

Workup

  1. customAfter this time the reaction mixture was evaporated
  2. customthe residue purified by silica gel flash chromatography with 30%

Sources & evidence

ORD record
ord-8212fd3c7e1f4d92800be5df5e46ecce
Source dataset
uspto-grants-2015_01
Patent number
US08927546B2

Reaction notes

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