Diisopropylethylamine → tert-butyl 4-{3-[(3R)-3-{[1-(5-bromopyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

HRID 526343Notes

Reaction equation

HRID 526343 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24](O)=[O:25])[CH2:19]2)=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:51][O:52][C:53](=[O:64])[CH2:54][CH:55]([NH2:63])[C:56]1[CH:57]=[N:58][CH:59]=[C:60]([Br:62])[CH:61]=1.C(N(C(C)C)C(C)C)C>CN(C)C=O.O>[Br:62][C:60]1[CH:61]=[C:56]([CH:55]([NH:63][C:24]([C@@H:20]2[CH2:21][CH2:22][CH2:23][N:18]([C:16](=[O:17])[CH2:15][CH2:14][CH:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:9][CH2:10]3)[CH2:19]2)=[O:25])[CH2:54][C:53]([O:52][CH3:51])=[O:64])[CH:57]=[N:58][CH:59]=1

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 54408184(R)-1-(3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl]-3-piperidinecarboxylic acid2×HCID 57045437Methyl 3-amino-3-(5-bromopyridin-3-yl)propanoate

Product 1

HCID 71259830tert-butyl 4-{3-[(3R)-3-{[1-(5-bromopyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylateYield 104%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

3.324 g (9.02 mmol) (3R)-1-{3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propanoyl}piperidine-3-carboxylic acid (Bioorg. Med. Chem. 13 (2005) 4343-4352, Compound 10) were suspended in 52 ml N,N-dimethylformamide and cooled to 0° C. 3.694 g (9.71 mmol) HATU, a solution of 1.798 g (6.94 mmol) 3-amino-3-(5-bromo-pyridin-3-yl)-propionic acid methyl ester in 78 ml N,N-dimethylformamide and 3.56 ml (20.82 mmol) N-ethyl-diisopropylamine were added. The mixture was stirred at 0° C. for 5 minutes and at room temperature for 24 hours. 160 ml water were added and the mixture extracted with 280 ml dichloromethane. The organic phase was washed with water, dried over sodium sulfate and concentrated in vacuum. Chromatography over 55 g basic silica gel (dichloromethane/ethanol 100/0-97/3-94/6) gave 4395 mg (104%) tert-butyl 4-{3-[(3R)-3-{[1-(5-bromopyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate.

Workup

  1. extractionthe mixture extracted with 280 ml dichloromethane
  2. washThe organic phase was washed with water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-823fd45a61b548babd7651ed9c5a55ea
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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