1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → {6-[5-(3-Trifluoromethoxy-phenyl)-pent-4-ynoylamino]-indol-1-yl}-acetic acid ethyl ester

HRID 751205Notes

Reaction equation

HRID 751205 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([NH2:15])[CH:13]=2)[CH:8]=[CH:7]1)[CH3:2].[F:17][C:18]([F:34])([F:33])[O:19][C:20]1[CH:21]=[C:22]([C:26]#[C:27][CH2:28][CH2:29][C:30](O)=[O:31])[CH:23]=[CH:24][CH:25]=1.Cl.CN(C)CCCN=C=NCC>CN(C)C1C=CN=CC=1.ClCCl>[CH2:1]([O:3][C:4](=[O:16])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([NH:15][C:30](=[O:31])[CH2:29][CH2:28][C:27]#[C:26][C:22]3[CH:23]=[CH:24][CH:25]=[C:20]([O:19][C:18]([F:33])([F:34])[F:17])[CH:21]=3)[CH:13]=2)[CH:8]=[CH:7]1)[CH3:2]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 16731704Ethyl 2-(6-amino-1H-indol-1-yl)acetateHCID 688226644-Pentynoic acid, 5-[3-(trifluoromethoxy)phenyl]-

Product 1

HCID 69275123{6-[5-(3-Trifluoromethoxy-phenyl)-pent-4-ynoylamino]-indol-1-yl}-acetic acid ethyl esterYield 75%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of (6-amino-indol-1-yl)-acetic acid ethyl ester (100 mg, 0.46 mmol; WO 2003041714 A1), 5-(3-trifluoromethoxy-phenyl)-pent-4-ynoic acid (115 mg, 0.44 mmol), 1-[3-(dimethylamino)-propyl]-3-ethylcarbodiimide hydrochloride (90 mg, 0.46 mmol) and 4-(dimethylamino)pyridine (57 mg, 0.46 mmol) in dichloromethane (1.5 ml) was stirred for 14 h at ambient temperature. The reaction mixture was diluted with dichloromethane, successively washed with 1 N HCl, brine, 1 N NaOH and brine, and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue purified by flash chromatography (silica gel, heptane/AcOEt) to give 152 mg (0.33 mmol, 72%) of the title compound as off-white crystals.

Workup

  1. washsuccessively washed with 1 N HCl, brine, 1 N NaOH and brine
  2. dry with materialdried over sodium sulfate
  3. customThe solvent was removed under reduced pressure
  4. customthe residue purified by flash chromatography (silica gel, heptane/AcOEt)

Sources & evidence

ORD record
ord-fcfc4445d5d2416183880753ee147b69
Source dataset
uspto-grants-2008_07
Patent number
US07405236B2

Reaction notes

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