Trifluoroacetic acid → 2-{4-[1-Benzyl-4-(2,4-difluoro-benzylamino)-pyrrolidine-2-carbonyl]-piperazin-1-yl}-benzonitrile

HRID 490594Notes

Reaction equation

HRID 490594 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([N:13](C(OC(C)(C)C)=O)[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[F:22])[CH2:10][CH:9]1[C:30](O)=[O:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[N:55]1([C:61]2[CH:68]=[CH:67][CH:66]=[CH:65][C:62]=2[C:63]#[N:64])[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]1.FC(F)(F)C(O)=O>ClCCl.C(N(CC)CC)C>[CH2:1]([N:8]1[CH2:12][CH:11]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[F:22])[CH2:10][CH:9]1[C:30]([N:58]1[CH2:59][CH2:60][N:55]([C:61]2[CH:68]=[CH:67][CH:66]=[CH:65][C:62]=2[C:63]#[N:64])[CH2:56][CH2:57]1)=[O:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2735875N-(2-Cyanophenyl)piperazineHCID 675474701-Benzyl-4-[tert-butoxycarbonyl-(2,4-difluoro-benzyl)-amino]-pyrrolidine-2-carboxylic acid

Product 1

HCID 675472242-{4-[1-Benzyl-4-(2,4-difluoro-benzylamino)-pyrrolidine-2-carbonyl]-piperazin-1-yl}-benzonitrileYield 9.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

The mixture of 1-benzyl-4-[tert-butoxycarbonyl-(2,4-difluoro-benzyl)-amino]-pyrrolidine-2-carboxylic acid (60.0 mg, 0.134 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (50.0 mg, 0.268 mmol), N-hydroxybenzotriazole (19.0 mg, 0.134 mmol), and 2-piperazin-1-yl-benzonitrile (46.7 mg, 0.25 mmol), triethylamine (0.05 ml) in dry dichloromethane (2 ml) was stirred overnight at rt, and then treated with trifluoroacetic acid (1 mL). The resulting mixture was stirred at room temperature for another 5 h and concentrated. The residue was purified by preparative HPLC on reversed phase eluting with an acetonitrile/water [0.1% aq NH3 (25%)] gradient to afford the title compound (6.7 mg, 9.7%) as a light yellow oil. MS m/e=516.4 [M+H]+.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for another 5 h
  2. concentrationconcentrated
  3. customThe residue was purified by preparative HPLC on reversed phase
  4. washeluting with an acetonitrile/water [0.1% aq NH3 (25%)] gradient

Sources & evidence

ORD record
ord-73e66cd60ddc44dfa9c452cd8c9eeba4
Source dataset
uspto-grants-2009_05
Patent number
US07528136B2

Reaction notes

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