Acetonitrile → HCID 22221501, compound

HRID 1794221Notes

Reaction equation

HRID 1794221 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([N:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)=[N:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:22][C:23]1[NH:27][C:26]2[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=2[N:24]=1.C(#N)C.[NH4+].[OH-]>CN(C=O)C.C(N(CC)CC)C.CO.C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([N:15]2[CH2:20][CH2:19][N:18]([CH2:22][C:23]3[NH:27][C:26]4[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=4[N:24]=3)[CH2:17][CH2:16]2)=[N:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 6342AcetonitrileHCID 14923Ammonium HydroxideHCID 785712-ChloromethylbenzimidazoleHCID 222215041-[5-(Benzyloxy)pyridin-2-yl]piperazine

Product 1

HCID 22221501HCID 22221501, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
23 °C

Procedure

The product from Example 29C and 2-chloromethyl-1H-benzoimidazole (0.88 mg) were combined and dissolved in DMF (7 mL)/triethylamine (1.5 mL). After stirring at 23° C. for 2 hours, the mixture was treated with acetonitrile (20 mL) and then allowed to stir for 24 hours. The reaction mixture was partitioned between CH2Cl2 (100 mL)/n-butanol (5 mL) and water (800 mL)/NH4OH (5 mL). The organic phase was separated, dried over Na2SO4, filtered, and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography to provide the title as a white solid (1.169 g (55%). mp 62–64° C.; Rf=0.26 (95:5 CH2Cl2:methanol:0.1% NH4OH); MS 400 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 12.3 (bs, NH, 1H), 7.90 (d, 1H, J=3 Hz), 7.55 (m, 1H), 7.3–7.5 (m, 8H), 7.15 (m, 2H), 6.80 (d, 1H, J=9 Hz), 5.05 (s, 2H), 3.76 (s, 2H), 3.39 (t, 4H, J=5.1 Hz), 2.57 (t, 4H, J=5.1 Hz).

Workup

  1. stirringto stir for 24 hours
  2. customThe reaction mixture was partitioned between CH2Cl2 (100 mL)/n-butanol (5 mL) and water (800 mL)/NH4OH (5 mL)
  3. customThe organic phase was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customThe residue was purified by flash chromatography
  8. customto provide the title as a white solid (1.169 g (55%)

Sources & evidence

ORD record
ord-5c4417a49b7e436c93ba885fd968f836
Source dataset
uspto-grants-2006_04
Patent number
US07022728B2

Reaction notes

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