Cyclopropylamine → 4-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-2-cyclopropylamino-3,5,6-trifluorobenzoic acid benzyl ester

HRID 10291

Reaction equation

HRID 10291 reaction equation
[CH2:1]([O:8][C:9](=[O:33])[C:10]1[C:15]([F:16])=[C:14]([F:17])[C:13]([N:18]2[CH2:22][CH2:21][C@H:20]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19]2)=[C:12]([F:31])[C:11]=1F)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:34]1([NH2:37])[CH2:36][CH2:35]1>CS(C)=O>[CH2:1]([O:8][C:9](=[O:33])[C:10]1[C:15]([F:16])=[C:14]([F:17])[C:13]([N:18]2[CH2:22][CH2:21][C@H:20]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:28])[CH3:29])=[O:25])[CH2:19]2)=[C:12]([F:31])[C:11]=1[NH:37][CH:34]1[CH2:36][CH2:35]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 69828CyclopropylamineHCID 86607128(S)-3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl-2,3,5,6-tetrafluorobenzoic acid benzyl ester

Product 1

HCID 866071294-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-2-cyclopropylamino-3,5,6-trifluorobenzoic acid benzyl esterYield 86.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 4-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-2,3,5,6-tetrafluorobenzoic acid benzyl ester (Example 2d, 2.5 g, 5.3 mmol), cyclopropylamine (40 mL, 577 mmol), and dimethyl sulfoxide (20 mL) in a sealed glass tube is heated at 80° C. for 24 hours. The excess amine is removed by blowing in compressed air, and the solution is then concentrated under high vacuum. The residue is purified by column chromatography (1:1:7 ethyl acetate/chloroform/hexanes) to afford the title compound as a solid (2.31 g). 1H NMR (CDCl3): δ 7.47–7.27 (m, 5H), 7.12 (bs, 1H), 5.30 (s, 2H), 4.78–4.62 (m, 1H), 4.35–4.17 (m, 1H), 3.96–3.56 (m, 3H), 3.54–3.39 (m, 1H), 2.91–2.73 (m, 1H), 2.24–2.02 (m, 1H), 1.96–1.77 (m, 1H), 1.45 (s, 9H), 0.69–0.56 (m, 2H), 0.53–0.40 (m, 2H).

Workup

  1. customThe excess amine is removed
  2. concentrationthe solution is then concentrated under high vacuum
  3. customThe residue is purified by column chromatography (1:1:7 ethyl acetate/chloroform/hexanes)

Sources & evidence

ORD record
ord-bafe96c800354c5393ce9d00526fb0c7
Source dataset
uspto-grants-2006_08
Patent number
US07094780B1

Linked notes

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