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

HRID 526351Notes

Reaction equation

HRID 526351 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:46]=[CH:47][C:48]=1[F:49])[CH2:6][O:7][C:8]1[CH:9]=[C:10]([C@@H:14]([NH:20][C:21]([C@@H:23]2[CH2:28][CH2:27][CH2:26][N:25]([C:29](=[O:45])[CH2:30][CH2:31][CH:32]3[CH2:37][CH2:36][N:35](C(OC(C)(C)C)=O)[CH2:34][CH2:33]3)[CH2:24]2)=[O:22])[CH2:15][C:16]([O:18]C)=[O:17])[CH:11]=[N:12][CH:13]=1)#[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:4]=[C:5]([CH:46]=[CH:47][C:48]=1[F:49])[CH2:6][O:7][C:8]1[CH:9]=[C:10]([C@H:14]([NH:20][C:21]([C@H:23]2[CH2:28][CH2:27][CH2:26][N:25]([C:29](=[O:45])[CH2:30][CH2:31][CH:32]3[CH2:33][CH2:34][NH:35][CH2:36][CH2:37]3)[CH2:24]2)=[O:22])[CH2:15][C:16]([OH:18])=[O:17])[CH:11]=[N:12][CH:13]=1)#[N:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 17749109Barium hydroxide, octahydrateHCID 71259840tert-butyl 4-{3-[(3R)-3-{[(1S)-1-{5-[(3-cyano-4-fluorobenzyl)oxy]pyridin-3-yl}-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Product 1

HCID 71258503(3R)-3-{5-[(3-cyano-4-fluorobenzyl)oxy]pyridin-3-yl}-3-[({(3S)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acidYield 14.1%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

Tert-butyl 4-{3-[(3R)-3-{[(1S)-1-{5-[(3-cyano-4-fluorobenzyl)oxy]pyridin-3-yl}-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (3.2 mg, 10 μmol) as solved in tert.-butanol (0.15 mL) and methanol (0.13 mL) and barium hydroxide octahydrate (7.4 mg, 20 μmol) was added. After stirring for 45 minutes at room temperature the solvent was distilled off at 0° C. by high vacuum. The residue was solved in water (0.3 mL) and acidified by formic acid (0.9 mL). After 3 hours at room temperature the solvent was distilled off at 0° C. by high vacuum and the residue was purified by preparative HPLC to yield 0.8 mg of (3R)-3-{5-[(3-cyano-4-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 3 hours at room temperature the solvent was distilled off at 0° C. by high vacuum
  3. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-eac6359dc81f4530b4e62a6e892816b4
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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