Cyclopropylamine → 4-[3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-2-cyclopropylamino-3-fluorobenzoic acid ethyl ester

HRID 10294Notes

Reaction equation

HRID 10294 reaction equation
[CH2:1]([O:3][C:4](=[O:26])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:15][CH2:14][CH:13]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]2)=[C:7]([F:24])[C:6]=1F)[CH3:2].[CH:27]1([NH2:30])[CH2:29][CH2:28]1>CN(C)C(=O)C>[CH2:1]([O:3][C:4](=[O:26])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:15][CH2:14][CH:13]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]2)=[C:7]([F:24])[C:6]=1[NH:30][CH:27]1[CH2:29][CH2:28]1)[CH3:2]

Participants

4

Reactant 2

HCID 69828CyclopropylamineHCID 210411774-[3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-2,3-difluorobenzoic acid ethyl ester

Product 1

HCID 210411824-[3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-2-cyclopropylamino-3-fluorobenzoic acid ethyl esterYield 76.9%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A solution of 4-[3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-2,3-difluorobenzoic acid ethyl ester (Example 2h, 1.85 g, 5.01 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 (1.57 g). 1H NMR (CDCl3): δ 7.59 (bs, 1H), 7.57 (dd, 1H), 6.00 (dd, 1H), 4.82–4.68 (bd, 1H), 4.39–4.18 (m, 3H), 3.80–3.49 (m, 3H), 3.41–3.30 (m, 1H), 3.00–2.88 (m, 1H), 2.31–2.11 (m, 1H), 2.00–1.85 (m, 1H), 1.45 (s, 9H), 1.37 (t, 3H), 0.73–0.50 (m, 4H).

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-c69cc9c8887b40f49bc3a26eadc7f8aa
Source dataset
uspto-grants-2006_08
Patent number
US07094780B1

Reaction notes

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