[(3R,1S)-3-(1H-1,2,4-Triazol-1-ylmethyl)cyclopentyl-N-BOC-amino]acetic acid → (2S,4S)-1-{2-[(3R,1S)-3-(1H-1,2,4-Triazol-1-ylmethyl)cyclopentyl-N-BOC-amino]acetyl}-4-fluoropyrrolidine-2-carbonitrile

HRID 1367111Notes

Reaction equation

HRID 1367111 reaction equation
[N:1]1([CH2:6][C@@H:7]2[CH2:11][CH2:10][C@H:9]([N:12]([CH2:20][C:21](O)=[O:22])[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8]2)[CH:5]=[N:4][CH:3]=[N:2]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[F:35][C@@H:36]1[CH2:40][NH:39][C@H:38]([C:41]#[N:42])[CH2:37]1>>[N:1]1([CH2:6][C@@H:7]2[CH2:11][CH2:10][C@H:9]([N:12]([CH2:20][C:21]([N:39]3[CH2:40][C@@H:36]([F:35])[CH2:37][C@H:38]3[C:41]#[N:42])=[O:22])[C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH2:8]2)[CH:5]=[N:4][CH:3]=[N:2]1

Participants

3

Reactant 2

HCID 66924331[(3R,1S)-3-(1H-1,2,4-Triazol-1-ylmethyl)cyclopentyl-N-BOC-amino]acetic acidHCID 72699082(2S,4S)-4-Fluoropyrrolidine-2-carbonitrile 4-methylbenzenesulfonate

Product 1

HCID 66924170(2S,4S)-1-{2-[(3R,1S)-3-(1H-1,2,4-Triazol-1-ylmethyl)cyclopentyl-N-BOC-amino]acetyl}-4-fluoropyrrolidine-2-carbonitrileYield 92.4%

Procedure

This compound was prepared from [(3R,1S)-3-(1H-1,2,4-Triazol-1-ylmethyl)cyclopentyl-N—BOC-amino]acetic acid (50 g, 154.14 mmol) and (2S,4S)-4-fluoropyrrolidine-2-carbonitrile p-toluenesulfonate (52.96 g, 184.96 mmol) as described in the preparation of its enantiomer (Method C) to give 59.9 g of the product as a white solid; 1H NMR (300 MHz, CDCl3) δ 1.22-1.36 (m, 2H), 1.44 (s, 9H), 1.62-1.81 (m, 2H), 1.88-2.04 (m, 3H), 2.22-2.27 (m, 1H), 2.34-2.49 (m, 1H), 2.62-2.77 (m, 1H), 3.69-4.01 (m, 3H), 4.13-4.23 (m, 3H), 4.99 (d, J=9.3 Hz, 1H), 5.33 (d, J=51.7 Hz, 0.3H, rotomer), 5.45 (d, J=51.0 Hz, 0.7H. rotomer), 7.92 (s, 1H), 8.08 (s, 0.4H, rotomer), 8.10 (s, 0.6H, rotomer).

Workup

  1. customas described in the preparation of its enantiomer (Method C)

Sources & evidence

ORD record
ord-3c791798c7b541cd8152a413367360ee
Source dataset
uspto-grants-2011_02
Patent number
US07893103B2

Reaction notes

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