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

HRID 252116Notes

Reaction equation

HRID 252116 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

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].

Workup

  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

Sources & evidence

ORD record
ord-9b4826f8e58f4bb9bcfda0156a4796a7
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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