Hydrochloric Acid → 3-[(2-Acetylamino-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester

HRID 73176ノート

反応式

HRID 73176 の反応式
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:8][C:9]=1[N:10]([C:14]([CH:16]1[CH2:21][CH2:20][CH:19]([CH3:22])[CH2:18][CH:17]1[N:23]=[N+]=[N-])=[O:15])[CH:11]([CH3:13])[CH3:12])=[O:4].Cl.[H][H].N1C=CC=CC=1.[C:41](OC(=O)C)(=[O:43])[CH3:42]>CO.[Pd].ClCCl.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:8][C:9]=1[N:10]([C:14]([CH:16]1[CH2:21][CH2:20][CH:19]([CH3:22])[CH2:18][CH:17]1[NH:23][C:41](=[O:43])[CH3:42])=[O:15])[CH:11]([CH3:13])[CH3:12])=[O:4]

参加物

10

反応物 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 7918Acetic AnhydrideHCID 597523943-[(2-Azido-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl esterHCID 178418361HCID 178418361、化合物

生成物 1

HCID 597523653-[(2-Acetylamino-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester収率 47%

試薬・触媒・溶媒 4

HCID 142844-(Dimethylamino)pyridine触媒HCID 23938Palladium触媒HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

To 3-[(2-Azido-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (17.5 mg, 0.04 mmol) in methanol (400 ul) was added concentrated hydrochloric acid (15 ul) followed by 10% palladium on charcoal (4 mg, 0.004 mmol). The reaction vessel was introduced with 20 psi of hydrogen and then stirred at room temperature for 17 hours. The residue was then filtered off through celite, washed with methanol and evaporated to give the crude product. To the crude product in dichloromethane (400 ul) was added pyridine (19 ul, 0.24 mmol), followed by acetic anhydride (15 ul, 0.16 mmol) and a catalytic amount of DMAP. The resulting solution was stirred for 24 hours at room temperature and then quenched with a saturated solution of NaHCO3 (5 ml). The aqueous phase was separated and washed with dichloromethane (2×5 ml). The combined organic layers were dried (Na2SO4), filtered and concentrated. The residue was then purified by preparative chromatography (60% EtOAc/Hexane) to obtain 8.5 mg (47% for two steps) of 3-[(2-Acetylamino-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester.

後処理

  1. filtrationThe residue was then filtered off through celite
  2. washwashed with methanol
  3. customevaporated
  4. customto give the crude product
  5. stirringThe resulting solution was stirred for 24 hours at room temperature
  6. customquenched with a saturated solution of NaHCO3 (5 ml)
  7. customThe aqueous phase was separated
  8. washwashed with dichloromethane (2×5 ml)
  9. dry with materialThe combined organic layers were dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was then purified by preparative chromatography (60% EtOAc/Hexane)

出典と根拠

ORDレコード
ord-158da6bab9f44b2782f21359dda4519a
出典データセット
uspto-grants-2014_09
特許番号
US08829030B2

反応ノート

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