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

HRID 252116노트

반응식

HRID 252116 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 887Methanol용매2회

실험 절차

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].

후처리

  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

출처 및 근거

ORD 기록
ord-9b4826f8e58f4bb9bcfda0156a4796a7
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07868014B2

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