Cyclopropylamine → HCID 21041183, compound

HRID 10295Notes

Reaction equation

HRID 10295 reaction equation
[CH2:1]([O:3][C:4](=[O:27])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([N:12]2[CH2:16][CH2:15][CH: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>CN(C)C(=O)C>[CH2:1]([O:3][C:4](=[O:27])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([N:12]2[CH2:16][CH2:15][CH: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]=1[NH:31][CH:28]1[CH2:30][CH2:29]1)[CH3:2]

Participants

4

Reactant 2

HCID 69828CyclopropylamineHCID 866071314-[3-(Tert-butoxycarbonylamino)pyrrolidin-1-yl]-5-chloro-2,3-difluorobenzoic acid ethyl ester

Product 1

HCID 21041183HCID 21041183, compoundYield 48.7%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A solution of 4-[3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-5-chloro-2,3-difluorobenzoic acid ethyl ester (Example 21, 3.75 g, 9.3 mmol) and cyclopropylamine (14.0 mL, 201 mmol) in N,N-dimethylacetamide (5 mL) is heated in a sealed glass tube for 48 hours at 100° C. The solution is then concentrated under high vacuum and purified by column chromatography (1:9 ethyl acetate/hexanes) to afford the title compound (2.0 g). 1H NMR (CDCl3): δ 7.64 (d, 1H), 7.56 (bs, 1H), 4.98–4.90 (bd, 1H), 4.40–4.20 (m, 3H), 3.78–3.63 (m, 4H), 2.97–2.83 (m, 1H), 2.35–2.21 (m, 1H), 1.93–1.81 (m, 1H), 1.46 (s, 9H), 1.38 (t, 3H), 0.75–0.61 (m, 2H), 0.57–0.50 (m, 2H).

Workup

  1. concentrationThe solution is then concentrated under high vacuum
  2. custompurified by column chromatography (1:9 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-04ac14ea81ab4703950b7e11ba716028
Source dataset
uspto-grants-2006_08
Patent number
US07094780B1

Reaction notes

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