Ammonia → (S)-2-[3-(2,4-Dichlorobenzylamino)-pyrrolidin-1-yl]-pyrimidine-5-carbonitrile

HRID 252140Notes

Reaction equation

HRID 252140 reaction equation
[Cl:1][C:2]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:3]=1[CH2:4][NH:5][C@H:6]1[CH2:10][CH2:9][N:8]([C:11]2[N:16]=[CH:15][C:14](Br)=[CH:13][N:12]=2)[CH2:7]1.N.[CH3:24][N:25](C)C=O>ClCCl.[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:1][C:2]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:3]=1[CH2:4][NH:5][C@H:6]1[CH2:10][CH2:9][N:8]([C:11]2[N:16]=[CH:15][C:14]([C:24]#[N:25])=[CH:13][N:12]=2)[CH2:7]1

Participants

7

Reactant 3

HCID 222AmmoniaHCID 6228DimethylformamideHCID 11503055(3S)-1-(5-bromopyrimidin-2-yl)-N-[(2,4-dichlorophenyl)methyl]pyrrolidin-3-amine

Product 1

HCID 59860367(S)-2-[3-(2,4-Dichlorobenzylamino)-pyrrolidin-1-yl]-pyrimidine-5-carbonitrileYield 36%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

Add zinc cyanide (104 mg, 0.88 mmol) and tetrakis(triphenylphosphine) palladium(0) (209 mg, 0.18 mmol) to a stirred solution of (S)-(2,4-dichlorobenzyl)-[1-(5-bromopyrimidin-2-yl)-pyrrolidin-3-yl]-amine (359 mg, 0.89 mmol) in N,N-dimethylformamide (5 mL). Heat at 65° C. for 4 hours. Cool to room temperature and add 2 M aqueous ammonia solution (30 mL). Extract with ethyl acetate (3×50 mL), extract the combined organic layers with water (5×50 mL) followed by saturated aqueous sodium chloride (50 mL). Concentrate to give a residue. Dissolve the residue in dichloromethane, filter, and concentrate to give a residue. Chromatograph the residue on silica gel to give the title compound as a white solid (111 mg, 36%). 1H NMR (400 MHz, CDCl3) δ 8.50 (2H, m), 7.32-7.40 (2H, m), 7.20-7.27 (1H, m), 3.86-3.94 (2H, m), 3.75-3.83 (2H, m), 3.63-3.71 (1H, m), 3.48-3.55 (2H, m), 2.20 (1H, m), 1.95 (1H, m); MS (ES): m/z=348 [M+].

Workup

  1. temperatureCool to room temperature
  2. extractionExtract with ethyl acetate (3×50 mL)
  3. extractionextract the combined organic layers with water (5×50 mL)
  4. concentrationConcentrate
  5. customto give a residue
  6. filtrationfilter
  7. concentrationconcentrate
  8. customto give a residue

Sources & evidence

ORD record
ord-9591ddd1cd27402383ea97224c45bba2
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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