Methanol → (3R)-3-{5-[(4-cyano-3-fluorobenzyl)oxy]pyridin-3-yl}-3-[({(3S)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acid

HRID 526353Notes

Reaction equation

HRID 526353 reaction equation
[C:1]([C:3]1[CH:48]=[CH:47][C:6]([CH2:7][O:8][C:9]2[CH:10]=[C:11]([C@@H:15]([NH:21][C:22]([C@@H:24]3[CH2:29][CH2:28][CH2:27][N:26]([C:30](=[O:46])[CH2:31][CH2:32][CH:33]4[CH2:38][CH2:37][N:36](C(OC(C)(C)C)=O)[CH2:35][CH2:34]4)[CH2:25]3)=[O:23])[CH2:16][C:17]([O:19]C)=[O:18])[CH:12]=[N:13][CH:14]=2)=[CH:5][C:4]=1[F:49])#[N:2].CO.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-]>C(O)(C)(C)C>[C:1]([C:3]1[CH:48]=[CH:47][C:6]([CH2:7][O:8][C:9]2[CH:10]=[C:11]([C@H:15]([NH:21][C:22]([C@H:24]3[CH2:29][CH2:28][CH2:27][N:26]([C:30](=[O:46])[CH2:31][CH2:32][CH:33]4[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]4)[CH2:25]3)=[O:23])[CH2:16][C:17]([OH:19])=[O:18])[CH:12]=[N:13][CH:14]=2)=[CH:5][C:4]=1[F:49])#[N:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 17749109Barium hydroxide, octahydrateHCID 71258934Tert-butyl 4-{3-[(3R)-3-{[(1S)-1-(5-(4-cyano-3-fluorobenzyloxy)pyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Product 1

HCID 71259067(3R)-3-{5-[(4-cyano-3-fluorobenzyl)oxy]pyridin-3-yl}-3-[({(3S)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acidYield 47.1%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

Tert-butyl 4-{3-[(3R)-3-{[(1S)-1-(5-(4-cyano-3-fluorobenzyloxy)pyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (10 mg, 15 μmol) as solved in tert.-butanol (0.6 mL) and methanol (0.6 mL) and barium hydroxide octahydrate (23 mg, 74 μmol) was added. After stirring for 45 minutes room temperature the solvent was distilled off at 0° C. by high vacuum. The residue was acidified with formic acid (1 mL). After 18 hours at 5° C. the solvent was distilled off at 0° C. by high vacuum and the residue was purified by preparative HPLC to yield 4 mg of (3R)-3-{5-[(4-cyano-3-fluorobenzyl)oxy]pyridin-3-yl}-3-[({(3S)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acid.

Workup

  1. distillationwas distilled off at 0° C. by high vacuum
  2. distillationAfter 18 hours at 5° C. the solvent was distilled off at 0° C. by high vacuum
  3. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-1da1354882564db9a5401ab104f9a9c1
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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