Oxalyl chloride → 2-[1-(4-Chlorophenyl)cyclopropanecarboxamido]-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide

HRID 1483213

反応式

HRID 1483213 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([OH:13])=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.C(N(C(C)C)CC)(C)C.[NH2:29][C:30]1[S:40][C:33]2[CH2:34][N:35]([CH2:38][CH3:39])[CH2:36][CH2:37][C:32]=2[C:31]=1[C:41]([NH2:43])=[O:42]>C(Cl)Cl.CN(C)C=O.O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:11]([NH:29][C:30]3[S:40][C:33]4[CH2:34][N:35]([CH2:38][CH3:39])[CH2:36][CH2:37][C:32]=4[C:31]=3[C:41]([NH2:43])=[O:42])=[O:13])[CH2:9][CH2:10]2)=[CH:6][CH:7]=1

参加物

8

反応物 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 986061-(p-Chlorophenyl)cyclopropanecarboxylic acidHCID 6144392-Amino-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide

生成物 1

HCID 1183073052-[1-(4-Chlorophenyl)cyclopropanecarboxamido]-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide収率 32.3%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 1-(4-chlorophenyl)cyclopropanecarboxylic acid (K1, 131 mg, 0.666 mmol) in anhydrous methylene chloride (3 mL) was added oxalyl chloride (0.100 mL, 1.17 mmol) followed by 2 drops of N,N-dimethylformamide at room temperature under nitrogen. After stirring at room temperature for 1 h, the reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in anhydrous tetrahydrofuran (3 mL). To the resulting solution was added diisopropylethylamine (0.200 mL, 1.12 mmol) followed by a suspension of compound F4 (150 mg, 0.666 mmol) in anhydrous tetrahydrofuran (3 mL). After stirring at room temperature for 3 h, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified by flash column chromatography on silica gel eluting with methylene chloride to methanol/methylene chloride (1:19). Further purification by trituration with acetonitrile gave compound K2 as a light yellow solid (87 mg, 32%): 1H NMR (500 MHz, CDCl3) δ 11.79 (bs, 1H), 7.47-7.42 (s, 4H), 5.56 (bs, 2H), 3.57 (s, 2H), 2.82-2.77 (m, 4H), 2.62 (q, J=7.0 Hz, 2H), 1.78-1.74 (m, 2H), 1.20-1.12 (m, 5H). MS (M+H) 404.

後処理

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. dissolutionThe resulting residue was dissolved in anhydrous tetrahydrofuran (3 mL)
  3. stirringAfter stirring at room temperature for 3 h
  4. concentrationthe reaction mixture was concentrated under reduced pressure
  5. customthe resulting residue was purified by flash column chromatography on silica gel eluting with methylene chloride to methanol/methylene chloride (1:19)
  6. customFurther purification by trituration with acetonitrile

出典と根拠

ORDレコード
ord-39729f04acc145deba2f3c0232bdca13
出典データセット
uspto-grants-2016_08
特許番号
US09416141B2

関連ノート

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