benzyl 2-((1R,2S)-2-((R)-5-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-2-methoxy-5, 6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopropyl)acetate → (2-(((5R)-5-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-2-methoxy-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)carbonyl)cyclopropyl)acetic acid

HRID 2202269Notes

Reaction equation

HRID 2202269 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:13][C:14]([C@@H:16]2[N:25]([C:26]([C@H:28]3[CH2:30][C@@H:29]3[CH2:31][C:32]([O:34]CC3C=CC=CC=3)=[O:33])=[O:27])[CH2:24][CH2:23][C:22]3[N:21]=[C:20]([O:42][CH3:43])[CH:19]=[CH:18][C:17]2=3)=[O:15])[CH:5]=[C:6]([F:12])[C:7]=1[Si:8]([CH3:11])([CH3:10])[CH3:9]>CO.[C].[Pd]>[F:1][C:2]1[CH:3]=[C:4]([NH:13][C:14]([C@@H:16]2[N:25]([C:26]([CH:28]3[CH2:30][CH:29]3[CH2:31][C:32]([OH:34])=[O:33])=[O:27])[CH2:24][CH2:23][C:22]3[N:21]=[C:20]([O:42][CH3:43])[CH:19]=[CH:18][C:17]2=3)=[O:15])[CH:5]=[C:6]([F:12])[C:7]=1[Si:8]([CH3:11])([CH3:9])[CH3:10]

Participants

4

Reactant 1

HCID 131735742benzyl 2-((1R,2S)-2-((R)-5-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-2-methoxy-5, 6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopropyl)acetate

Product 1

HCID 131735744(2-(((5R)-5-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-2-methoxy-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)carbonyl)cyclopropyl)acetic acidYield 80%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 887MethanolSolvent

Procedure

A mixture of benzyl 2-((1R,2S)-2-((R)-5-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-2-methoxy-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopropyl)acetate (46 mg, 0.08 mmol) and 10% palladium-carbon (8.06 mg, 0.08 mmol, 50%, wet) in MeOH (15 mL) was stirred at room temperature for 2 hr under hydrogen atmosphere (1 atm). The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 30→100% ethyl acetate/hexane) to give the title compound (31.2 mg, 0.060 mmol, 80%) as a white solid.

Workup

  1. customThe catalyst was removed by filtration
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 30→100% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b2bbad063cc44241b46baebcf6fbf408
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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