o-Phenetidine → HCID 11956628, compound

HRID 1170873Notes

Reaction equation

HRID 1170873 reaction equation
[CH2:1]([N:5]([C:18](=[O:26])[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=1)[C:6]1[N:7]=[C:8]2[CH2:13][CH2:12][CH2:11][CH2:10][N:9]2[C:14]=1[C:15](O)=[O:16])[CH2:2][CH2:3][CH3:4].CCN=C=N[CH2:32][CH2:33][CH2:34][N:35](C)C.C1C=NC2N(O)N=NC=2C=1.[CH3:48][CH2:49][O:50][C:51]1C(N)=C[CH:54]=[CH:55][CH:56]=1>C(Cl)Cl>[CH2:49]([O:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:32][C:33]=1[CH2:34][NH:35][C:15]([C:14]1[N:9]2[CH2:10][CH2:11][CH2:12][CH2:13][C:8]2=[N:7][C:6]=1[N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[C:18](=[O:26])[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=1)=[O:16])[CH3:48]

Participants

6

Reactant 4

HCID 7203o-PhenetidineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 57465090HCID 57465090, compound

Product 1

HCID 11956628HCID 11956628, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-[butyl-(3-chloro-benzoyl)-amino]-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridine-3-carboxylic acid (130 mg, 0.45 mmol), EDCI (72.9 mg, 0.38 mmol, 1.0 eq.) and HOAt (4.7 mg, 0.035 mmol, 0.1 eq.) were dissolved in DCM (3.5 mL). ortho-phenetidine (51.5 μL, 0.35 mmol) was added thereto and the solution was stirred for 16 hours at room temperature. The solvent was removed under vacuum, EtOAc (30 mL) was added thereto and the organic phase was washed a plurality of times with a 0.5 M solution of KHSO4 in water (30 mL) and saturated aqueous NaHCO3 solution (35 mL). The aqueous phases were shaken out a plurality of times with ethyl acetate. The combined organic phases were washed with saturated aqueous NaCl solution (40 mL) and dried over sodium sulphate, and the solvent was removed under vacuum. The untreated product was purified by column chromatography (SiO2, DCM→DCM/MeOH 98/2). 130 mg (73%) of the desired product 2-[butyl-(3-chloro-benzoyl)-amino]-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridine-3-carboxylic acid were obtained.

Workup

  1. customThe solvent was removed under vacuum, EtOAc (30 mL)
  2. additionwas added
  3. washthe organic phase was washed a plurality of times with a 0.5 M solution of KHSO4 in water (30 mL) and saturated aqueous NaHCO3 solution (35 mL)
  4. stirringThe aqueous phases were shaken out a plurality of times with ethyl acetate
  5. washThe combined organic phases were washed with saturated aqueous NaCl solution (40 mL)
  6. dry with materialdried over sodium sulphate
  7. customthe solvent was removed under vacuum
  8. customThe untreated product was purified by column chromatography (SiO2, DCM→DCM/MeOH 98/2)

Sources & evidence

ORD record
ord-0709546b1cf044f082b33e5eff598cc2
Source dataset
uspto-grants-2010_11
Patent number
US07829568B2

Reaction notes

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