1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-N-(6-Fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide

HRID 1961377Notes

Reaction equation

C(OC([N:8]1[CH2:12][CH2:11][CH2:10][C@@:9]1([CH3:16])[C:13]([OH:15])=O)=O)(C)(C)C.[F:17][C:18]1[N:23]=[CH:22][C:21]([NH2:24])=[CH:20][CH:19]=1.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>CN1CCCC1=O>[F:17][C:18]1[N:23]=[CH:22][C:21]([NH:24][C:13]([C@:9]2([CH3:16])[CH2:10][CH2:11][CH2:12][NH:8]2)=[O:15])=[CH:20][CH:19]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a stirred solution of (5)-1-(tert-butoxycarbonyl)-2-methylpyrrolidine-2-carboxylic acid (1.0 g, 4.37 mmol) and 6-fluoropyridin-3-amine (1.47 g, 13.1 mmol), 1-hydroxybenzotriazole (0.65 mg, 4.81 mmol), and N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide (2.5 g, 13.1 mmol) in N-methylpyrrolidinone (10 mL) was added diisopropylethylamine (3.8 mL, 21.8 mmol). The reaction mixture was heated to 65° C. for 12 h and the solvent was evaporated to dryness. The residue was separated by preparative HPLC. The crude product was dissolved in methanol and 4N HCl in dioxane (4 mL) was added. The reaction mixture was stirred at room temperature overnight and the crude product was used in the next step without further purification. LC/MS [M+H]+: 224; Ret time (Method F): 0.78 min.

Workup

customthe solvent was evaporated to dryness
customThe residue was separated by preparative HPLC
dissolutionThe crude product was dissolved in methanol
addition4N HCl in dioxane (4 mL) was added
customthe crude product was used in the next step without further purification
custom0.78 min.

Sources & evidence

ORD record: ord-0e5787db47444ff19c26f8631e4f81a0
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415340B2

Reaction notes

Loading…