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

HRID 526358Notes

Reaction equation

HRID 526358 reaction equation
C([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(OC(C)(C)C)=O)[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][CH:20]=[C:19]([O:23][CH2:24][CH2:25][F:26])[CH:18]=2)[CH:14]=1)(C)(C)C>C(O)=O>[F:26][CH2:25][CH2:24][O:23][C:19]1[CH:18]=[C:17]([C:16]#[C:15][C:13]2[CH:14]=[C:9]([C@@H:8]([NH:27][C:28]([C@@H:30]3[CH2:35][CH2:34][CH2:33][N:32]([C:36](=[O:52])[CH2:37][CH2:38][CH:39]4[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]4)[CH2:31]3)=[O:29])[CH2:7][C:6]([OH:53])=[O:5])[CH:10]=[N:11][CH:12]=2)[CH:22]=[CH:21][CH:20]=1

Participants

3

Reactant 1

HCID 71609424tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{[3-(2-fluoroethoxy)phenyl]ethynyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Product 1

HCID 71609468(3S)-3-(5-{[3-(2-fluoroethoxy)phenyl]ethynyl}pyridin-3-yl)-3-[({(3R)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acidYield 82.9%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

Tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{[3-(2-fluoroethoxy)phenyl]ethynyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (15.7 mg, 20 μmol) was heated to 60° C. in formic acid (1.5 mL) for 40 minutes. The solution was then concentrated in vacuum and the residue purified by preparative HPLC to yield 9.6 mg of (3S)-3-(5-{[3-(2-fluoroethoxy)phenyl]ethynyl}pyridin-3-yl)-3-[({(3R)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acid.

Workup

  1. concentrationThe solution was then concentrated in vacuum
  2. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-baa9a2d20e814085b46a034ca666ad2b
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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