Toluene → tert-butyl 4-{3-[(3R)-3-{[(1S)-1-(5-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}pyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

HRID 526333Notes

Reaction equation

HRID 526333 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:39])[NH:25][C@H:26]([C:32]3[CH:33]=[N:34][CH:35]=[C:36]([OH:38])[CH:37]=3)[CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH2:19]2)=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].CC1C=CC(S(O[CH2:57][CH2:58][O:59][CH2:60][CH2:61][O:62][CH2:63][CH2:64][F:65])(=O)=O)=CC=1.C1(C)C=CC=CC=1>CN(C=O)C>[F:65][CH2:64][CH2:63][O:62][CH2:61][CH2:60][O:59][CH2:58][CH2:57][O:38][C:36]1[CH:37]=[C:32]([C@@H:26]([NH:25][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[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:13][CH2:12]3)[CH2:19]2)=[O:39])[CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH:33]=[N:34][CH:35]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 595523472-[2-(2-Fluoroethoxy)ethoxy]ethyl 4-methylbenzene-1-sulfonateHCID 71259055tert-butyl-4-{3-[(3R)-3-{[(1S)-1-(5-hydroxypyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Product 1

HCID 71609268tert-butyl 4-{3-[(3R)-3-{[(1S)-1-(5-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}pyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylateYield 40.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To tert-butyl-4-{3-[(3R)-3-{[(1S)-1-(5-hydroxypyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (30 mg, 60 μmol) in DMF (7.6 mL) was added cesium carbonate (44.7 mg, 140 μmol) and 2-[2-(2-fluoroethoxy)ethoxy]ethyl 4-methylbenzenesulfonate (25 mg, 80 μmol) while stirring at room temperature. After 5 hours toluene was added and the mixture was concentrated in vacuum. The DMF free residue was purified by preparative thin layer chromatography on silica gel (ethyl acetate) to yield 16.7 mg of tert-butyl 4-{3-[(3R)-3-{[(1S)-1-(5-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}pyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate.

Workup

  1. concentrationthe mixture was concentrated in vacuum
  2. customThe DMF free residue was purified by preparative thin layer chromatography on silica gel (ethyl acetate)

Sources & evidence

ORD record
ord-d1f75b901b34446fa442ceec3a941bf8
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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