Triethylamine → (S)-[1-(6-Fluoropyridin-3-yl)-pyrrolidin-3-yl]-(2-bromo-4-chlorobenzyl)-amine

HRID 252116ノート

反応式

HRID 252116 の反応式
[Br:1][C:2]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:3]=1[CH:4]=O.Cl.[F:12][C:13]1[N:18]=[CH:17][C:16]([N:19]2[CH2:23][CH2:22][C@H:21]([NH2:24])[CH2:20]2)=[CH:15][CH:14]=1.C(N(CC)CC)C.[BH4-].[Na+]>CO>[F:12][C:13]1[N:18]=[CH:17][C:16]([N:19]2[CH2:23][CH2:22][C@H:21]([NH:24][CH2:4][C:3]3[CH:6]=[CH:7][C:8]([Cl:10])=[CH:9][C:2]=3[Br:1])[CH2:20]2)=[CH:15][CH:14]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 131547102-Bromo-4-chlorobenzaldehydeHCID 66854645(S)-1-(6-fluoropyridin-3-yl)-pyrrolidin-3-ylamine hydrochloride

生成物 1

HCID 59860344(S)-[1-(6-Fluoropyridin-3-yl)-pyrrolidin-3-yl]-(2-bromo-4-chlorobenzyl)-amine

試薬・触媒・溶媒 1

HCID 887Methanol溶媒2 回

実験手順

Add 2-bromo-4-chlorobenzaldehyde (159 mg, 0.73 mmol) to a solution of (S)-1-(6-fluoropyridin-3-yl)-pyrrolidin-3-ylamine hydrochloride (144 mg, 0.66 mmol) and triethylamine (292 μL, 2.1 mmol) in methanol (5 mL). Stir the resulting mixture for 18 h. Add sodium borohydride (80 mg, 2.1 mmol). Stir for 1 h. Dilute the reaction mixture with methanol (10 mL) and pour onto a column of Dowex® 50Wx2 (H+ form). Rinse the column with methanol then elute the product with 5% triethylamine in methanol. Concentrate and dissolve the residue in methanol. Dilute with acetonitrile and concentrate to give the title compound as a oil. Dissolve the oil in methanol and add excess 1 N HCl in methanol. Concentrate to dryness and crystallize from methanol/acetonitrile to give the title compound as its hydrochloride salt, an off white solid (84 mg, 30%). Elemental analysis calculated for C16H17BrCl2FN3: C, 45.63; H, 4.07; N, 9.98. Found: C, 45.39; H, 4.02; N, 9.85. MS (ES): m/z=386 [M+H].

後処理

  1. stirringStir for 1 h
  2. additionpour onto a column of Dowex® 50Wx2 (H+ form)
  3. washRinse the column with methanol
  4. washthen elute the product with 5% triethylamine in methanol
  5. concentrationConcentrate
  6. dissolutiondissolve the residue in methanol
  7. additionDilute with acetonitrile
  8. concentrationconcentrate

出典と根拠

ORDレコード
ord-9b4826f8e58f4bb9bcfda0156a4796a7
出典データセット
uspto-grants-2011_01
特許番号
US07868014B2

反応ノート

読み込み中…