Sodium hydride → 6-Bromo-1-(cyclopentylmethyl)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine

HRID 2205896ノート

反応式

HRID 2205896 の反応式
[H-].[Na+].[Br:3][C:4]1[N:9]=[CH:8][C:7]2[CH:10]=[C:11]([C:13]3[CH:14]=[N:15][N:16]([CH3:18])[CH:17]=3)[NH:12][C:6]=2[CH:5]=1.Br[CH2:20][CH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1>CN(C=O)C.O.CCOC(C)=O>[Br:3][C:4]1[N:9]=[CH:8][C:7]2[CH:10]=[C:11]([C:13]3[CH:14]=[N:15][N:16]([CH3:18])[CH:17]=3)[N:12]([CH2:20][CH:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)[C:6]=2[CH:5]=1

参加物

7

反応物 3

HCID 24758Sodium hydride2 回HCID 12723264(Bromomethyl)cyclopentaneHCID 867062766-Bromo-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine

生成物 1

HCID 867063066-Bromo-1-(cyclopentylmethyl)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine収率 69.6%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

Sodium hydride (60% in mineral oil, 10.8 mg, 0.271 mmol) was added to a solution of 6-bromo-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine (Preparation 22, 50 mg, 0.180 mmol) in DMF (780 mL). The reaction mixture was then stirred for 15 minutes at room temperature before the addition of (bromomethyl)cyclopentane (44 mg, 0.271 mmol). The reaction mixture was then stirred overnight at room temperature and for 24 hours at 60° C. Sodium hydride (60% in mineral oil, 5 mg, 0.125 mmol) was added and the reaction was stirred for another 7 hours at 60° C. The reaction mixture was then diluted with water and EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude was purified via Biotage silica gel column chromatography eluting with (DCM/EtOAc 99/1 to 80/20) to afford the title product as a colourless oil (45 mg, 69%). 1H NMR (500 MHz, CDCl3) d 1.10-1.19 (m, 2H), 1.46-1.64 (m, 6H), 2.24-2.33 (m, 1H), 4.03 (s, 3H), 4.09 (d, J=7.6 Hz, 2H), 6.53 (d, J=0.9 Hz, 1H), 7.45 (t, J=0.9 Hz, 1H), 7.59 (s, 1H), 7.68 (s, 1H), 8.60 (d, J=0.9 Hz, 1H). LC (Method B)-MS (ESI, m/z) tR 3.03 min, 359 [(M+H+), 100%].

後処理

  1. stirringthe reaction was stirred for another 7 hours at 60° C
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude was purified via Biotage silica gel column chromatography
  8. washeluting with (DCM/EtOAc 99/1 to 80/20)

出典と根拠

ORDレコード
ord-c19fe1eedc4b4f939967d2b887926095
出典データセット
uspto-grants-2016_06
特許番号
US09371319B2

反応ノート

読み込み中…