Ammonia → HCID 178458084, compound

HRID 1424196Notes

Reaction equation

HRID 1424196 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:15]1[NH:19][C:18]2[CH:20]=[CH:21][C:22]([C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:23][C:17]=2[N:16]=1)[CH:10]([CH3:14])[C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.C([O-])(O)=O.[Na+].[NH3:48]>C1COCC1.CN(C=O)C.O1CCOCC1.N1C=CC=CC=1>[NH2:48][C:11](=[O:13])[CH:10]([CH3:14])[C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])[C:15]1[NH:19][C:18]2[CH:20]=[CH:21][C:22]([C:24]([CH3:25])([CH3:27])[CH3:26])=[CH:23][C:17]=2[N:16]=1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 178460520HCID 178460520, compound

Product 1

HCID 178458084HCID 178458084, compound

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 312751,4-DioxaneSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

A mixture of (3S)-3-[(tert-butoxycarbonyl)amino]-3-(5-tert-butyl-1H-benzimidazol-2-yl)-2-methylpropanoic acid (Preparation 30, 7.25 g, 19.33 mmol), Boc2O (5.9 g, 27.0 mmol), pyridine (1 mL) and NaHCO3 (2 g, 25 mmol) in THF/DMF (200 mL/100 mL) was stirred at room temperature for 18 hours. 0.5M Ammonia in dioxane (150 mL) was added and the reaction continued stirring at room temperature for a further 18 hours. The reaction was concentrated to dryness and diluted with saturated aqueous NaHCO3 solution. The solution was extracted with 2-MethylTHF and concentrated in vacuo. The residue was purified using reverse phase column chromatography eluting with 5-70% acetonitrile in 0.1% formic acid in water to afford the title compound as a mixture of diastereomers (3 g, 43%).

Workup

  1. stirringthe reaction continued stirring at room temperature for a further 18 hours
  2. concentrationThe reaction was concentrated to dryness
  3. additiondiluted with saturated aqueous NaHCO3 solution
  4. extractionThe solution was extracted with 2-MethylTHF and
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified
  7. washeluting with 5-70% acetonitrile in 0.1% formic acid in water

Sources & evidence

ORD record
ord-00a03b1021054958b6a86a5a69b9e8ed
Source dataset
uspto-grants-2015_01
Patent number
US08927587B2

Reaction notes

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