Diisopropylethylamine → 3-[4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-butyronitrile

HRID 1257613ノート

反応式

HRID 1257613 の反応式
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[C:18](Cl)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:23][CH:24]1[CH2:29][CH2:28][N:27]([CH:30]([CH3:34])[CH2:31][C:32]#[N:33])[CH2:26][CH2:25]1.C(N(C(C)C)CC)(C)C>CC(O)C>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[C:18]([NH:23][CH:24]4[CH2:29][CH2:28][N:27]([CH:30]([CH3:34])[CH2:31][C:32]#[N:33])[CH2:26][CH2:25]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 583947741-(benzenesulfonyl)-4-chloro-5-nitro-1H-pyrrolo(2,3-b)pyridineHCID 609133153-(4-Amino-piperidin-1-yl)-butyronitrile

生成物 1

HCID 673427783-[4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-butyronitrile収率 53.1%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
80 °C

実験手順

A mixture of 1-benzenesulfonyl-4-chloro-5-nitro-1H-pyrrolo[2,3-b]pyridine (15.33 g, 45.4 mmol), 3-(4-amino-piperidin-1-yl)-butyronitrile (hydrochloride salt) (50.0 mmol), diisopropylethylamine (24.5 ml, 141 mmol) in propan-2-ol (200 ml) was heated at 80° C. for 18 h. The mixture was cooled to 25° C. and was concentrated to approximately 25 ml volume. This material was partitioned between water (200 ml) and CH2Cl2 (2×200 ml). The combined organic layers were dried over MgSO4, filtered, and the filtrate was concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (gradient: 0 to 6% CH3OH in CH2Cl2) afforded 3-[4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-butyronitrile (11.3 g, 53% over 3 steps) as a yellow-orange foam. LCMS (Method G, ESI): RT=0.70 min, m+H=469.3. This material was used in the next step below without additional characterization.

後処理

  1. temperatureThe mixture was cooled to 25° C.
  2. concentrationwas concentrated to approximately 25 ml volume
  3. customThis material was partitioned between water (200 ml) and CH2Cl2 (2×200 ml)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customPurification of the residue by column chromatography on silica gel (gradient: 0 to 6% CH3OH in CH2Cl2)

出典と根拠

ORDレコード
ord-6cfee8aa200c4324af1cebf93103048e
出典データセット
uspto-grants-2013_06
特許番号
US08461328B2

反応ノート

読み込み中…