4-Hydroxybenzaldehyde → HCID 86756689, compound

HRID 1976966Notes

Reaction equation

HRID 1976966 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:33])[C@H:5]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][NH:28]2)=[O:26])=[CH:20][CH:19]=1)[NH:6]C(=O)C1C(C)=CC=CC=1Cl.CCN(C(C)C)C(C)C.[OH:43][C:44]1[CH:51]=[CH:50][C:47]([CH:48]=O)=[CH:46][CH:45]=1>C1COCC1>[CH3:2][O:3][C:4](=[O:33])[C@H:5]([CH2:17][C:18]1[CH:19]=[CH:20][C:21]([N:24]2[C:25](=[O:26])[C@@H:27]3[CH2:32][CH2:31][CH2:30][CH2:29][N:28]3[CH:48]2[C:47]2[CH:50]=[CH:51][C:44]([OH:43])=[CH:45][CH:46]=2)=[CH:22][CH:23]=1)[NH2:6]

Participants

5

Reactant 3

HCID 1264-HydroxybenzaldehydeHCID 81531DiisopropylethylamineHCID 69848800HCID 69848800, compound

Product 1

HCID 86756689HCID 86756689, compoundYield 15.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

(S)-N-(2-chloro-6-methylbenzoyl)-4-[[(2-piperidinyl)carbonyl]amino]-L-phenylalanine methyl ester hydrochloride (100 mg, 0.2 mmol), DIPEA (0.10 mL, 0.54 mmol) and 4-hydroxybenzaldehyde (30 mg, 0.25 mmol) was added to a suspension of activated 3 Å molecular sieves (100 mg) in THF (1.5 mL). The resulting mixture was stirred room temperature overnight and at 60° C. for 3 hr. After it was cooled to room temperature, the mixture was transferred onto a silica gel column and eluted with ethyl acetate:hexane (2:1) to give N-[(2-chloro-6-methylphenyl)carbonyl]]-4-[(8aS)-hexahydro-3-(4-hydroxyphenyl)-1-oxoimidazo[1.5-a]pyridin-2-yl]-L-phenylalanine methyl ester (17.5 mg, 0.031 mmol) as a foam. The methyl ester (17.5 mg, 0.031 mmol) was hydrolyzed with 1N NaOH (0.1 mL, 0.1 mmol) in 0.5 mL of ethanol at room temperature for 6 hr. The reaction mixture was acidified to pH<2 with TFA and was purified on RP-HPLC to give N-[(2-chloro-6-methylphenyl)carbonyl]-4-[(8aS)-hexahydro-3-(4-hydroxyphenyl)-1-oxoimidazo[1.5-a]pyridin-2-yl]-L-phenylalanine (8.3 mg, 0.015 mmol), in 7.5% yield. HRMS: calcd. 548.1952. Obs. 548.1938 (M+H).

Workup

  1. temperatureAfter it was cooled to room temperature
  2. washeluted with ethyl acetate:hexane (2:1)

Sources & evidence

ORD record
ord-4f30bc6e69f24654b4dcef0353f19453
Source dataset
uspto-grants-2001_05
Patent number
US06229011B1

Reaction notes

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