Hydrochloric Acid → (S)-Benzyl 2-((3-chloropyrazin-2-yl)methylcarbamoyl)pyrrolidine-1-carboxylate

HRID 928293Notes

Reaction equation

[Cl:1][C:2]1[C:3]([CH2:8][NH2:9])=[N:4][CH:5]=[CH:6][N:7]=1.Cl.[N:11]1([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[CH2:18][CH2:17][CH2:16][C@H:12]1[C:13](O)=[O:14].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[Cl:1][C:2]1[C:3]([CH2:8][NH:9][C:13]([C@@H:12]2[CH2:16][CH2:17][CH2:18][N:11]2[C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])=[O:14])=[N:4][CH:5]=[CH:6][N:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (3-chloropyrazin-2-yl)methanamine.HCl (9.57 g, 21.26 mmol, 40% wt) and Z-Pro-OH (5.3 g, 21.26 mmol) in dichloromethane (250 mL) was added triethylamine (11.85 mL, 85 mmol) and the reaction mixture was cooled to 0° C. After 15 min stirring at 0° C., HATU (8.49 g, 22.33 mmol) was added. The mixture was stirred for 1 hour at 0° C. and then overnight at room temperature. The mixture was washed with 0.1 M HCl-solution, 5% NaHCO3, water and brine, dried over sodium sulfate and concentrated in vacuo. The product was purified using silica gel chromatography (heptane/ethyl acetate=1/4 v/v %) to give 5 g of (S)-benzyl 2-((3-chloropyrazin-2-yl)methylcarbamoyl)pyrrolidine-1-carboxylate (62.7%).

Workup

stirringThe mixture was stirred for 1 hour at 0° C.
customovernight
customat room temperature
washThe mixture was washed with 0.1 M HCl-solution, 5% NaHCO3, water and brine
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
customThe product was purified

Sources & evidence

ORD record: ord-c91da49ad5bd449ea66f4ee38d342cfe
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290504B2

Reaction notes

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