Triethylamine → HCID 178496464, compound

HRID 724320Notes

Reaction equation

HRID 724320 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10](=[O:27])[C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[N:13][C:12]=2[O:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([S:25][CH3:26])[CH:20]=2)[CH2:5][CH2:4]1.C(N(CC)CC)C.[CH3:35][O:36][CH2:37][C:38](O)=[O:39].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[F:17][C:15]1[CH:14]=[N:13][C:12]([O:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([S:25][CH3:26])[CH:20]=2)=[C:11]([CH:16]=1)[C:10]([NH:9][C@H:6]1[CH2:7][CH2:8][C@@H:3]([NH:2][C:38](=[O:39])[CH2:37][O:36][CH3:35])[CH2:4][CH2:5]1)=[O:27]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 12251Methoxyacetic AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178503208HCID 178503208, compound

Product 1

HCID 178496464HCID 178496464, compoundYield 68.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(cis-4-Amino-cyclohexyl)-5-fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinamide hydrochloride (150 mg, 0.364 mmol) was dissolved in dimethylformamide (3 ml) and triethylamine (153 μl, 1.1 mmol) was added followed by methoxyacetic acid (31 μl, 0.40 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (77 mg, 0.40 mmol) and 1-hydroxybenzotriazole (54 mg, 0.40 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 (3×10 ml). The combined organic extracts were washed with water (2×5 ml), brine (5 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 (95:5, by volume) and the product was triturated with diethylether (5 ml) to give 5-Fluoro-N-[cis-4-(2-methoxy-acetylamino)-cyclohexyl]-2-(3-methylsulfanyl-phenoxy)-nicotinamide (112 mg) as a white solid.

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 (3×10 ml)
  4. washThe combined organic extracts were washed with water (2×5 ml), brine (5 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:methanol (95:5, by volume)
  8. customthe product was triturated with diethylether (5 ml)

Sources & evidence

ORD record
ord-06cab441c02d4006a87903c382ebc34f
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

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