Triethylamine → HCID 178477280, compound

HRID 724333Notes

Reaction equation

HRID 724333 reaction equation
[CH2:1]([S:3][C:4]1[CH:5]=[C:6]([CH:18]=[CH:19][CH:20]=1)[O:7][C:8]1[N:16]=[CH:15][C:14]([F:17])=[CH:13][C:9]=1[C:10]([OH:12])=O)[CH3:2].Cl.[NH2:22][CH:23]1[CH2:28][CH2:27][CH:26]([NH:29][C:30](=[O:36])[C:31]([CH3:35])([CH3:34])[CH2:32][OH:33])[CH2:25][CH2:24]1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[CH2:1]([S:3][C:4]1[CH:5]=[C:6]([CH:18]=[CH:19][CH:20]=1)[O:7][C:8]1[N:16]=[CH:15][C:14]([F:17])=[CH:13][C:9]=1[C:10]([NH:22][C@H:23]1[CH2:24][CH2:25][C@H:26]([NH:29][C:30](=[O:36])[C:31]([CH3:34])([CH3:35])[CH2:32][OH:33])[CH2:27][CH2:28]1)=[O:12])[CH3:2]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21877127N-(4-amino-cyclohexyl)-3-hydroxy-2,2-dimethyl-propionamide hydrochlorideHCID 218771352-[3-(Ethylsulfanyl)phenoxy]-5-fluoronicotinic acid

Product 1

HCID 178477280HCID 178477280, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(3-Ethylsulfanyl-phenoxy)-5-fluoro-nicotinic acid (150 mg, 0.51 mmol) was added to a solution of N-(4-amino-cyclohexyl)-3-hydroxy-2,2-dimethyl-propionamide hydrochloride (80:20 cis:trans, 135 mg, 0.54 mmol) and triethylamine (0.21 ml, 1.5 mmol) in dimethylformamide (3 ml) under nitrogen at room temperature. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (108 mg, 0.56 mmol) followed by 1-hydroxybenzotriazole (76 mg, 0.56 mmol) were then added and the reaction was stirred at room temperature for 20 h. The mixture was concentrated under reduced pressure, partitioned between ethyl acetate (20 ml) and water (20 ml) and the organic phase was removed, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography on a silica gel eluting with a solvent gradient of dichloromethane:methanol (95:5) and the product was purified by preparative HPLC to give two products.

Workup

  1. additionwere then added
  2. concentrationThe mixture was concentrated under reduced pressure
  3. custompartitioned between ethyl acetate (20 ml) and water (20 ml)
  4. customthe organic phase was removed
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash column chromatography on a silica gel eluting with a solvent gradient of dichloromethane:methanol (95:5)
  8. customthe product was purified by preparative HPLC
  9. customto give two products

Sources & evidence

ORD record
ord-6bf41a25e3d7400ea611bc57bfaeceee
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

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