Triethylamine → Azd 7009

HRID 500506ノート

反応式

HRID 500506 の反応式
C([N:3](CC)CC)C.Br[CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15].[OH:19][C@@H:20]([CH2:31][N:32]1[CH2:39][CH:38]2[O:40][CH:34]([CH2:35][NH:36][CH2:37]2)[CH2:33]1)[CH2:21][O:22][C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=1>CN(C=O)C>[OH-:13].[NH4+:3].[C:27]([C:26]1[CH:25]=[CH:24][C:23]([O:22][CH2:21][C@@H:20]([OH:19])[CH2:31][N:32]2[CH2:33][CH:34]3[O:40][CH:38]([CH2:37][N:36]([CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:35]3)[CH2:39]2)=[CH:30][CH:29]=1)#[N:28]

参加物

6

反応物 3

HCID 8471TriethylamineHCID 4103526tert-Butyl N-(2-bromoethyl)carbamateHCID 684578084-{[(2S)-2-Hydroxy-3-(9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)propyl]-oxy}benzonitrile

生成物 2

HCID 14923Ammonium HydroxideHCID 9876235Azd 7009収率 37.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
40 °C

実験手順

Triethylamine (8.56 mL, 0.061 mol) and tert-butyl 2-bromoethylcarbamate (see Preparation R above, 11.0 g, 0.049 mol) were added to a solution of 4-{[(2S)-2-hydroxy-3-(9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)-propyl]oxy}benzonitrile (see preparation B above, 12.41 g, 0.038 mol) in DMF (100 mL). The mixture was stirred for 20 h at 40° C., then concentrated in vacuo. The residue was dissolved in chloroform (100 mL), and washed with saturated sodium chloride. The aqueous layer was separated and extracted with chloroform (2×150 mL). The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The crude brown oil was chromatographed (×2) on silica gel, eluting first with chloroform:methanol (9:1), then with chloroform:methanol:conc. ammonium hydroxide (9:1:0.05) to afford 4.13 g (24%) of the title compound.

後処理

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in chloroform (100 mL)
  3. washwashed with saturated sodium chloride
  4. customThe aqueous layer was separated
  5. extractionextracted with chloroform (2×150 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude brown oil was chromatographed (×2) on silica gel
  9. washeluting first with chloroform:methanol (9:1)

出典と根拠

ORDレコード
ord-a3a52f6fc8b7487497d6bf9f185a7615
出典データセット
uspto-grants-2010_08
特許番号
US07772229B2

反応ノート

読み込み中…