Tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{[4-(2-fluoroethoxy)phenyl]ethynyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate → tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{2-[4-(2-fluoroethoxy)phenyl]ethyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

HRID 526363Notes

Reaction equation

HRID 526363 reaction equation
[C:1]([O:5][C:6](=[O:53])[CH2:7][C@H:8]([NH:27][C:28]([C@@H:30]1[CH2:35][CH2:34][CH2:33][N:32]([C:36](=[O:52])[CH2:37][CH2:38][CH:39]2[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:41][CH2:40]2)[CH2:31]1)=[O:29])[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([C:15]#[C:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][F:26])=[CH:19][CH:18]=2)[CH:14]=1)([CH3:4])([CH3:3])[CH3:2]>C(OCC)(=O)C.CO.[Pd]>[C:1]([O:5][C:6](=[O:53])[CH2:7][C@H:8]([NH:27][C:28]([C@@H:30]1[CH2:35][CH2:34][CH2:33][N:32]([C:36](=[O:52])[CH2:37][CH2:38][CH:39]2[CH2:40][CH2:41][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:43][CH2:44]2)[CH2:31]1)=[O:29])[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][F:26])=[CH:19][CH:18]=2)[CH:14]=1)([CH3:2])([CH3:4])[CH3:3]

Participants

5

Reactant 1

HCID 71609423Tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{[4-(2-fluoroethoxy)phenyl]ethynyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Product 1

HCID 89407592tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{2-[4-(2-fluoroethoxy)phenyl]ethyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylateYield 62.7%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{[4-(2-fluoroethoxy)phenyl]ethynyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (20 mg, 30 μmol) in ethyl acetate (0.8 mL) and methanol (013 mL) was stirred for 4.45 hours at room temperature under a hydrogen atmosphere in the presence of palladium on charcoal (10%, 19 mg). The suspension was filtrated through celite, which were washed thoroughly with methanol. The solution was concentrated under reduced pressure and purified by preparative HPLC to yield 13.9 mg of tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{2-[4-(2-fluoroethoxy)phenyl]ethyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate.

Workup

  1. filtrationThe suspension was filtrated through celite, which
  2. washwere washed thoroughly with methanol
  3. concentrationThe solution was concentrated under reduced pressure
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-f05ba6c32667454d9c656705c7c8f987
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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