(2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrile → 1{(S)-2-[2-(2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-(S)-4-methyl-pentanoyl}-(S)-pyrrolidine-2-carboxylic acid amide

HRID 1869646Notes

Reaction equation

HRID 1869646 reaction equation
Br[CH2:2][C:3]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]#[N:11])=[O:4].[NH2:12][CH:13]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:14]([N:16]1[CH2:20][CH2:19][CH2:18][CH:17]1[C:21]([NH2:23])=[O:22])=[O:15]>C1COCC1>[C:10]([C@@H:6]1[CH2:7][CH2:8][CH2:9][N:5]1[C:3](=[O:4])[CH2:2][NH:12][C@@H:13]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:14]([N:16]1[CH2:20][CH2:19][CH2:18][C@H:17]1[C:21]([NH2:23])=[O:22])=[O:15])#[N:11]

Participants

4

Reactant 2

HCID 11031276(2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrileHCID 197622411-(2-Amino-4-methyl-pentanoyl)-pyrrolidine-2-carboxylic acid amide

Product 1

HCID 99289781{(S)-2-[2-(2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-(S)-4-methyl-pentanoyl}-(S)-pyrrolidine-2-carboxylic acid amideYield 74.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1-(2-bromo-acetyl)-(S)-pyrrolidine-2-carbonitrile (44 mg, 0.2 mmol) in THF (1 mL) was added slowly to a cold solution (−15° C.) of 1-(2-amino-4-methyl-pentanoyl)-pyrrolidine-2-carboxylic acid amide (55 mg, 0.24 mmol) in THF (2 mL). The temperature of the reaction mixture was gradually increased to room temperature. After stirring at this temperature overnight, the residue was concentrated and purified by LCMS to yield 1{(S)-2-[2-(2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-(S)-4-methyl-pentanoyl}-(S)-pyrrolidine-2-carboxylic acid amide (54 mg; 62%). This pure product (20 mg) was dissolved in THF (1 mL), HCl ether (0.1 mL; 2M) was added and the mixture was concentrated to give the HCl salt form of 1-{(S)-2-[2-(2-cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-(S)-4-methyl-pentanoyl}-(S)-pyrrolidine-2-carboxylic acid amide. 1H-NMR data (CDCl3—CD3OD, 20:1): δ, 8.25 and 6.25 (s, 1H each), 4.73 (m, 1H), 4.43 (t, 1H, J=5.4 Hz), 4.2 (d, 1H, J=14.1 Hz), 4.0-3.47 (m, 7H), 2.4-1.9 (m, 10H), 1.41 (m, 1H). MS: calculated for C18H29N5O3+H 364.2; found: 364.2.

Workup

  1. concentrationthe residue was concentrated
  2. custompurified by LCMS

Sources & evidence

ORD record
ord-bfd648cc78ae46c68e288b9739fdfe8b
Source dataset
uspto-grants-2009_12
Patent number
US07638638B2

Reaction notes

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