Benzonitrile, 4-chloro-3-nitro- → HCID 15462943, compound

HRID 1637703Notes

Reaction equation

HRID 1637703 reaction equation
[CH2:1]([CH:8]1[CH2:13][CH2:12][N:11]([C:14]([CH2:16][NH2:17])=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(C1CCN(C(C(Cl)Cl)=O)CC1)C1C=CC=CC=1.[N-]=[N+]=[N-].[Na+].Cl[C:41]1[CH:48]=[CH:47][C:44]([C:45]#[N:46])=[CH:43][C:42]=1[N+:49]([O-:51])=[O:50].C([O-])(O)=O.[Na+]>CC(C)=O.CN(C=O)C.[Pd]>[CH2:1]([CH:8]1[CH2:9][CH2:10][N:11]([C:14]([CH2:16][NH:17][C:41]2[CH:48]=[CH:47][C:44]([C:45]#[N:46])=[CH:43][C:42]=2[N+:49]([O-:51])=[O:50])=[O:15])[CH2:12][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 13655Benzonitrile, 4-chloro-3-nitro-HCID 33557Sodium AzideHCID 516892Sodium BicarbonateHCID 4251733(4-Benzylpiperidinecarbonyl)methylene chlorideHCID 11831311HCID 11831311, compound2×

Product 1

HCID 15462943HCID 15462943, compoundYield 49.2%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 180AcetoneSolventHCID 6228DimethylformamideSolvent

Procedure

(4-Benzylpiperidinecarbonyl)methylamine was made by treatment of (4-benzylpiperidinecarbonyl)methylene chloride with NaN3 in aqueous acetone, followed by hydrogenation with 5% Pd/C. Reaction of (4-benzylpiperidinecarbonyl)methylamine (8.6 mmol) with 4-chloro-3-nitro-benzonitrile (10 mmol) in DMF (10 mL) in the presence of NaHCO3 (10 mmol) at 100° C. for 16 hours gave 4-[(4-benzylpiperidinecarbonyl)methyl]amino-3-nitrobenzonitrile (1.6 g, 49.2% of yield), which was then hydrogenated in MeOH in the presence of 5% of Pd/C (10% w/w) to produce 1-(4-benzylpiperidinecarbonyl)methyl-6-cyanobenzimidazole (1.3 g, 90% of yield). 1-(4-Benzylpiperidinecarbonyl)methyl-6-cyanobenzimidazole (0.57 mmol) was then carried through the Pinner reaction, followed by purification on TLC plates with 10% MeOH in CH2Cl2, and further purification by HPLC to give the title compound: mp: 68-70° C.; 1H NMR (CD3OD) δ8.52 (s, 1H), 8.20 (s, 1H), 7.75 (s, 2H), 7.29-7.24 (m, 2H), 7.18-7.16 (m, 3H), 5.43 (dd, J=17.2 Hz, J=24.5 Hz, 2H), 4.40 (d, J=12.8 Hz, 1H), 4.00 (d, J=12.8 Hz, 1H), 3.18 (t, J=12.8 Hz, 1H), 2.68 (t, J=12.8 Hz, 1H), 2.59 (d, J=7.00 Hz, 2H), 1.87-1.78 (m, 2H), 1.72-1.68 (m, 1H, 1.42-1.35 (m, 1H), 1.22-1.15 (m, 1H); 13C NMR (CD3OD) δ168.76, 166.06, 148.73, 141.23, 139.50, 130.17, 129.45, 129.33, 127.35, 127.11, 124.04, 120.40, 113.19, 47.38, 46.36, 43.93, 43.73, 39.15, 33.35, 32.73; MS: 188.8 (M+2H)2+ ; HRMS:376.2130 (obs.), 376.2137 (calcd.); Anal.: (C22H25N5O1 +1.85TFA+0.18HCl+0.5H2O).

Sources & evidence

ORD record
ord-96e0e9b9c7f54effa3f5e1a5c50d245f
Source dataset
uspto-grants-2000_03
Patent number
US06043257

Reaction notes

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