Cyclopropylamine → 4-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-2-cyclopropylamino-3,6-difluorobenzoic acid ethyl ester

HRID 10289Notes

Reaction equation

HRID 10289 reaction equation
[CH2:1]([O:3][C:4](=[O:27])[C:5]1[C:10]([F:11])=[CH:9][C:8]([N:12]2[CH2:16][CH2:15][C@H:14]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]2)=[C:7]([F:25])[C:6]=1F)[CH3:2].[CH:28]1([NH2:31])[CH2:30][CH2:29]1>CS(C)=O>[CH2:1]([O:3][C:4](=[O:27])[C:5]1[C:10]([F:11])=[CH:9][C:8]([N:12]2[CH2:16][CH2:15][C@H:14]([NH:17][C:18]([O:20][C:21]([CH3:23])([CH3:24])[CH3:22])=[O:19])[CH2:13]2)=[C:7]([F:25])[C:6]=1[NH:31][CH:28]1[CH2:30][CH2:29]1)[CH3:2]

Participants

4

Reactant 2

HCID 69828CyclopropylamineHCID 586818974-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-2,3,6-trifluorobenzoic acid ethyl ester

Product 1

HCID 586818704-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-2-cyclopropylamino-3,6-difluorobenzoic acid ethyl esterYield 81.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 4-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-2,3,6-trifluorobenzoic acid ethyl ester (Example 2b, 5.4 g, 13.9 mmol), cyclopropylamine (40 mL, 577 mmol), and dimethyl sulfoxide (28 mL) in a sealed glass tube is heated at 100° C. for 27 hours. The excess amine is removed by blowing in compressed air before the solution is concentrated under high vacuum. The residue is then purified by column chromatography (1:1:8 ethyl acetate/chloroform/hexanes) to afford the title compound (4.80 g). 1H NMR (CDCl3): δ 7.42 (bs, 1H), 5.69 (ddd, 1H), 4.76–4.61 (m, 1H), 4.37–4.19 (m, 3H), 3.81–3.66 (m, 1H), 3.65–3.43 (m, 2H), 3.39–3.28 (m, 1H), 2.98–2.82 (m, 1H), 2.30–2.09 (m, 1H), 1.98–1.82 (m, 1H), 1.45 (s, 9H), 1.34 (t, 3H), 0.72–0.68 (m, 2H), 0.67–0.44 (m, 2H).

Workup

  1. customThe excess amine is removed
  2. concentrationis concentrated under high vacuum
  3. customThe residue is then purified by column chromatography (1:1:8 ethyl acetate/chloroform/hexanes)

Sources & evidence

ORD record
ord-57255046f53942d386f59bb285a97248
Source dataset
uspto-grants-2006_08
Patent number
US07094780B1

Reaction notes

Loading…