1,2-Dichloroethane → HCID 178522833, compound

HRID 843679Notes

Reaction equation

HRID 843679 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][C@@H:11]1[CH2:16][CH2:15][C@H:14]([C:17]([OH:19])=O)[CH2:13][CH2:12]1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.[F:34][C:35]1[CH:42]=[CH:41][CH:40]=[CH:39][C:36]=1[CH2:37][NH2:38]>CN(C=O)C>[F:34][C:35]1[CH:42]=[CH:41][CH:40]=[CH:39][C:36]=1[CH2:37][NH:38][C:17]([C@H:14]1[CH2:13][CH2:12][C@@H:11]([CH2:10][C:2]2[NH:1][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=2)[CH2:16][CH2:15]1)=[O:19]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 666492-FluorobenzylamineHCID 181649HOAtHCID 178525705HCID 178525705, compound

Product 1

HCID 178522833HCID 178522833, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (E) cis-4-(1H-benzimidazol-2-ylmethyl)-cyclohexanecarboxylic acid (271 mg, 1.05 mmol), EDC (200 mg, 1.05 mmol) and HOAt (142 mg, 1.05 mmol) in anhydrous DMF (4 mL) was added 2-fluorobenzylamine (131 mg, 1.05 mmol) and the reaction mixture was stirred for 1 h. The reaction mixture was partitioned between saturated aqueous NaHCO3 and EtOAc and the organic layer washed 2× with water. The EtOAc was dried with MgSO4 and concentrated to give a yellow solid. The crude material was triturated with 2:2:1 water/CH3CN/DMSO and the resultant white solid filtered off. Repetitive concentration and trituration of the filtrate in the same manner gave cis-4-(1H-benzimidazol-2-ylmethyl)-cyclohexanecarboxylic acid 2-fluoro-benzylamide (F) (230 mg, 60%) as a white solid. The (F) compound was stirred in 1M HCl/ether (10 mL) for 1 h and concentrated to give the HCl salt of Ex. 7 (250 mg): 1H NMR (400 MHz, CD3OD) δ 7.50 (br s 2 H), 7.35-7.25 (m, 2 H), 7.22-7.05 (m, 4 H), 4.43 (s, 2 H), 2.92 (d, 2 H), 2.41 (m, 1 H), 2.23 (m, 1 H), 1.93 (m, 2 H), 1.60 (m, 6 H); mass spectrum m/z 366 [(M+H)+; calcd for C22H25N3OF: 366].

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous NaHCO3 and EtOAc
  2. washthe organic layer washed 2× with water
  3. dry with materialThe EtOAc was dried with MgSO4
  4. concentrationconcentrated
  5. customto give a yellow solid
  6. customThe crude material was triturated with 2:2:1 water/CH3CN/DMSO
  7. filtrationthe resultant white solid filtered off
  8. concentrationRepetitive concentration and trituration of the filtrate in the same manner

Sources & evidence

ORD record
ord-1b53ce37dc1b4fd1a2ed0a9c3fe17907
Source dataset
uspto-grants-2002_04
Patent number
US06380205B1

Reaction notes

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