Triethylamine → HCID 178503227, compound

HRID 724307

Reaction equation

HRID 724307 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([S:18][CH3:19])[CH:13]=2)=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(N(CC)CC)C.Cl.[NH2:28][C@@H:29]1[CH2:34][CH2:33][C@H:32]([OH:35])[CH2:31][CH2:30]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[NH3:4].[F:1][C:2]1[CH:3]=[N:4][C:5]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([S:18][CH3:19])[CH:13]=2)=[C:6]([CH:10]=1)[C:7]([NH:28][C@H:29]1[CH2:34][CH2:33][C@@H:32]([OH:35])[CH2:31][CH2:30]1)=[O:9]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 113918232-[3-(Methylsulfanyl)phenoxy]-5-fluoronicotinic acidHCID 178479277HCID 178479277, compound

Product 2

HCID 222AmmoniaHCID 178503227HCID 178503227, compoundYield 163.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinic acid (100 mg, 0.358 mmol) was dissolved in dimethylformamide (2 ml) and triethylamine (150 mg, 1.07 mmol) was added followed by cis-4-aminocyclohexanol hydrochloride (54 mg, 0.358 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (76 mg, 0.394 mmol) and 1-hydroxybenzotriazole (53 mg, 0.394 mmol). The reaction was stirred under nitrogen at room temperature for 18 h and the solvent was removed under reduced pressure. The residue was partitioned between sat. sodium bicarbonate solution (5 ml) and ethyl acetate (10 ml) and the aqueous phase was extracted with ethyl acetate (2×10 ml). The combined organic extracts were washed with water (2×3 ml), brine (3 ml), dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:concentrated aqueous ammonia (98:2:0.2, by volume) to give 5-fluoro-N-(cis-4-hydroxy-cyclohexyl)-2-(3-methylsulfanyl-phenoxy)-nicotinamide (110 mg) as a white foam.

Workup

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was partitioned between sat. sodium bicarbonate solution (5 ml) and ethyl acetate (10 ml)
  3. extractionthe aqueous phase was extracted with ethyl acetate (2×10 ml)
  4. washThe combined organic extracts were washed with water (2×3 ml), brine (3 ml)
  5. dry with materialdried over MgSO4
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-e44cce910ed94f63a5f0be446c5579ca
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Linked notes

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