Hydrochloric Acid → {1-[2-(4'-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester

HRID 417551

Reaction equation

HRID 417551 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13](=[O:28])[NH:14][C:15]1[CH:16]=[C:17]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[CH:18]=[CH:19][CH:20]=1)=O)(C)(C)C.Cl.[CH3:30][O:31][C:32]([NH:34][CH:35]([CH:39]([CH3:41])[CH3:40])[C:36](O)=[O:37])=[O:33].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CO.CN(C=O)C.C(OCC)(=O)C>[CH3:30][O:31][C:32](=[O:33])[NH:34][CH:35]([C:36]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13](=[O:28])[NH:14][C:15]1[CH:16]=[C:17]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[CH:18]=[CH:19][CH:20]=1)=[O:37])[CH:39]([CH3:41])[CH3:40]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 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 666205302-(4'-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66621197{1-[2-(4'-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl esterYield 96.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

2-(4′-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.66 g, 4.14 mmol) was dissolved in methanol (20 mL) and concentrated HCl (4 mL) was added. The mixture was stirred at 50° C. for 80 min then cooled and concentrated. The residue was treated with 2-methoxycarbonylamino-3-methyl-butyric acid (870 mg, 4.97 mmol) and HATU (2.05 g, 5.38 mmol) and brought up in DMF (20 mL). The mixture was cooled to 0° C. and DIPEA (3.60 mL, 20.7 mmol). After 100 min, the reaction mixture was diluted with ethyl acetate (250 mL) and washed with water and brine. The organic phase was dried over magnesium sulfate and concentrated. The resulting residue was purified by silica column chromatography (50% to 80% EtOAc/hexanes) to afford {1-[2-(4′-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (1.83 g, 96% over 2 steps).

Workup

  1. temperaturethen cooled
  2. concentrationconcentrated
  3. temperatureThe mixture was cooled to 0° C.
  4. waitAfter 100 min
  5. washwashed with water and brine
  6. dry with materialThe organic phase was dried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe resulting residue was purified by silica column chromatography (50% to 80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-c0c88a86d8a445dbb28b0ab3d6a9026c
Source dataset
uspto-grants-2012_01
Patent number
US08088368B2

Linked notes

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