Hydrochloric Acid → 4-(4-{3-[4-(2-Aminopropionyl)piperazin-1-yl]propoxy}phenyl)-tetrahydropyran-4-carbonitrile

HRID 272910Notes

Reaction equation

HRID 272910 reaction equation
[N:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3([C:23]#[N:24])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C1C=[CH:27][C:28]2[N:33](O)N=N[C:29]=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.N1CCCCC1.[OH2:54]>C(Cl)Cl>[NH2:33][CH:28]([CH3:29])[C:27]([N:4]1[CH2:5][CH2:6][N:1]([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3([C:23]#[N:24])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:15][CH:16]=2)[CH2:2][CH2:3]1)=[O:54]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 962Water2×HCID 8082PiperidineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 598373994-[4-(3-Piperazin-1-ylpropoxy)phenyl]tetrahydropyran-4-carbonitrile

Product 1

HCID 685778634-(4-{3-[4-(2-Aminopropionyl)piperazin-1-yl]propoxy}phenyl)-tetrahydropyran-4-carbonitrileYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-[4-(3-piperazin-1-ylpropoxy)phenyl]tetrahydropyran-4-carbonitrile (265 mg, 0.81 mmol), DCM (10.6 ml), HOBT (120 mg, 0.89 mmol), FMoc (L)-aniline (277 mg, 0.89 mmol) and EDCl.HCl (171 mg, 0.89 mmol) were stirred at ambient temperature overnight. Water (10 ml) was added and stirred for one hour, the mixture was filtered and the organic phase separated and washed with water (10 ml), the organic phase was dried over MgSO4, filtered and concentrated in vacuo at 35° C. The residue was dissolved in DCM (9 ml) and piperidine (86 mg, 10 mmol) was added, the mixture was stirred at ambient temperature for one hour. To the reaction mixture, water (5 ml) was added and the organic phase separated, dried over MgSO4, filtered and concentrated in vacuo at 35° C. The crude material was subjected to chromatography on silica eluting with 2% MeOH in DCM to provide title compound (136 mg, 42%). 1H NMR (400 MHz, CDCl3), δ 7.38 (d, 2H), 6.93 (d, 2H), 4.11-4.05 (m, 2H), 4.03 (t, 2H), 3.89 (td, 2H), 3.77 (q, 1H), 3.65 (br s, 2H), 3.49 (br s, 2H), 2.55 (t, 2H), 2.45 (br s, 4H), 2.14-2.00 (m, 4H), 1.97 (m, 2H), 1.58 (br s, 2H), 1.25 (d, 3H).

Workup

  1. filtrationthe mixture was filtered
  2. customthe organic phase separated
  3. washwashed with water (10 ml)
  4. dry with materialthe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo at 35° C
  7. dissolutionThe residue was dissolved in DCM (9 ml)
  8. stirringthe mixture was stirred at ambient temperature for one hour
  9. customthe organic phase separated
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo at 35° C

Sources & evidence

ORD record
ord-ad90d5eea6c84839a0d0132c8ea2e690
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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