Dimethylformamide → methyl ((S)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate

HRID 1471006Notes

Reaction equation

HRID 1471006 reaction equation
Cl.[Br:2][C:3]1[NH:7][C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][NH:9]2)=[N:5][CH:4]=1.Cl.CN(C)[CH2:16][CH2:17][CH2:18]N=C=NCC.[OH2:25].ON1C2C=CC=CC=2N=N1.C[N:37]1[CH2:42][CH2:41][O:40]C[CH2:38]1.CN([CH:46]=[O:47])C>O>[Br:2][C:3]1[NH:7][C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:41](=[O:40])[C@@H:42]([NH:37][C:38](=[O:25])[O:47][CH3:46])[CH:17]([CH3:18])[CH3:16])=[N:5][CH:4]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 49780402(s)-5-Bromo-2-(pyrrolidin-2-yl)-1h-imidazole hydrochloride

Product 1

HCID 56605304methyl ((S)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamateYield 88%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of Example 126F (3.99 g, 15.8 mmol), Example 126A (2.77 g, 15.8 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (3.63 g, 19.0 mmol), 1-Hydroxy-benzotriazole hydrate (2.90 g, 19.0 mmol) and N-methylmorpholine (12.2 mL, 111.0 mmol) in DMF (150 mL) were allowed to stir overnight. Mixture was diluted with H2O and extracted with EtOAc (3×300 mL). The organic was washed with H2O and Brine. The organic was then dried (MgSO4), filtered and concentrated. Purification by chromatography (silica gel, 75% EtOAc in Hexanes) afforded 5.2 g (88%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.79 (dd, J=6.67, 3.63 Hz, 6H), 1.84-1.96 (m, 3H), 2.02-2.14 (m, 2H), 3.51 (s, 3H), 3.66-3.80 (m, 2H), 3.96-4.03 (m, 1H), 4.91-4.99 (m, 1H), 7.06 (d, J=1.52 Hz, 1H), 7.26 (d, J=8.46 Hz, 1H), 12.01 (s, 1H). MS (ESI) m/z 373 (M+H)+.

Workup

  1. extractionextracted with EtOAc (3×300 mL)
  2. washThe organic was washed with H2O and Brine
  3. dry with materialThe organic was then dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by chromatography (silica gel, 75% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-7ff3d983378b48ffb73698d9bd300f9c
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Reaction notes

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