Triethylamine → 2-[3-(ethylsulfanyl)phenoxy]-5-fluoro-N-[(1S,2R)-2-hydroxycyclohexyl]nicotinamide

HRID 724297ノート

反応式

HRID 724297 の反応式
[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].C(N(CC)CC)C.[NH2:28][C@H:29]1[CH2:34][CH2:33][CH2:32][CH2:31][C@H:30]1[OH:35].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[NH3:16].[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:28][C@H:29]1[CH2:34][CH2:33][CH2:32][CH2:31][C@H:30]1[OH:35])=[O:12])[CH3:2]

参加物

8

反応物 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6542151cis-2-AminocyclohexanolHCID 21877135HCID 21877135、化合物

生成物 2

HCID 222AmmoniaHCID 587462032-[3-(ethylsulfanyl)phenoxy]-5-fluoro-N-[(1S,2R)-2-hydroxycyclohexyl]nicotinamide収率 34.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

2-[3-(Ethylsulfanyl)phenoxy]-5-fluoronicotinic acid (250 mg, 0.85 mmol) was dissolved in dimethylformamide (5 ml) and triethylamine (475 μl, 3.41 mmol) was added followed by (1R,2S)-2-aminocyclohexanol hydroformate (144 mg, 0.89 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (180 mg, 0.94 mmol) and 1-hydroxybenzotriazole (127 mg, 0.94 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 water (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 brine (5 ml), dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography using dichloromethane:methanol:0.880 ammonia (98:2:0.2) as eluant to give 2-[3-(ethylsulfanyl)phenoxy]-5-fluoro-N-[(1S,2R)-2-hydroxycyclohexyl]nicotinamide (57 mg) as a colourless oil.

後処理

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was partitioned between water (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 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

出典と根拠

ORDレコード
ord-1358cfb99c9d464d99a7fc74bec414bd
出典データセット
uspto-grants-2006_11
特許番号
US07141586B2

反応ノート

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