Hydrochloric Acid → (1-{2-[5-(6-Bromonaphthalen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 1751486Notes

Reaction equation

HRID 1751486 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[C:23]([Br:28])[CH:24]=3)[CH:19]=2)=[CH:16][N:17]=1)=O)(C)(C)C.Cl.O1CCOCC1.[CH3:36][O:37][C:38]([NH:40][CH:41]([CH:45]([CH3:47])[CH3:46])[C:42](O)=[O:43])=[O:39].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[CH3:36][O:37][C:38](=[O:39])[NH:40][CH:41]([C:42]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[C:23]([Br:28])[CH:24]=3)[CH:19]=2)=[CH:16][N:17]=1)=[O:43])[CH:45]([CH3:47])[CH3:46]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 138211012-((Methoxycarbonyl)amino)-3-methylbutanoic acidHCID 58185449tert-butyl (2S)-2-[5-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl]pyrrolidine-1-carboxylate

Product 1

HCID 66620357(1-{2-[5-(6-Bromonaphthalen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl esterYield 99.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 2-[5-(6-Bromo-naphthalen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (6.4 g, 14.4 mmol) was added HCl in dioxane (36 mL, 144 mmol). The suspension was allowed to stir at room temperature for three hours. Upon completion by LCMS, the reaction was concentrated to dryness and the crude product (assumed 14.4 mmol) was suspended in dichloromethane. 2-Methoxycarbonylamino-3-methylbutyric acid (3.8 g, 21.7 mmol) and solid potassium phosphate (28.94 mmol) were added to the slurry. HATU (6.88 g, 18.08 mL) was added and the reaction was stirred at room temperature for 18 hours. Upon completion, the crude reaction was filtered through a sintered glass funnel. The supernate was concentrated in vacuo and purified by normal phase silica gel chromatography (20-70% Ethyl acetate (with 10% MeOH) in Hexanes) to give (1-{2-[5-(6-Bromo-naphthalen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (7.14 g, >90% yield) as a thick oil. LCMS-ESI+: calc'd for C24H27BrN4O3: 498.13 (M+); Found: 499.96 (M+H+).

Workup

  1. concentrationUpon completion by LCMS, the reaction was concentrated to dryness
  2. stirringthe reaction was stirred at room temperature for 18 hours
  3. customUpon completion, the crude reaction
  4. filtrationwas filtered through a sintered glass funnel
  5. concentrationThe supernate was concentrated in vacuo
  6. custompurified by normal phase silica gel chromatography (20-70% Ethyl acetate (with 10% MeOH) in Hexanes)

Sources & evidence

ORD record
ord-41a5a2166da345589c61cbae67dafda5
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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