Diphenylacetic Acid → (S)-5-diphenylacetyl-1-(3-methyl-4-nitrophenyl)methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid methyl ester

HRID 1609480Notes

Reaction equation

HRID 1609480 reaction equation
C1(N=C=NC2CCCCC2)CCCCC1.ON1C2C=CC=CC=2N=N1.[C:26]1([CH:32]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:33]([OH:35])=O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[CH3:42][O:43][C:44]([C@H:46]1[NH:51][CH2:50][C:49]2[N:52]=[CH:53][N:54]([CH2:55][C:56]3[CH:61]=[CH:60][C:59]([N+:62]([O-:64])=[O:63])=[C:58]([CH3:65])[CH:57]=3)[C:48]=2[CH2:47]1)=[O:45]>C(#N)C>[CH3:42][O:43][C:44]([C@H:46]1[N:51]([C:33](=[O:35])[CH:32]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH2:50][C:49]2[N:52]=[CH:53][N:54]([CH2:55][C:56]3[CH:61]=[CH:60][C:59]([N+:62]([O-:64])=[O:63])=[C:58]([CH3:65])[CH:57]=3)[C:48]=2[CH2:47]1)=[O:45]

Participants

6

Reactant 4

HCID 8333Diphenylacetic AcidHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 14457531(S)-1-(3-methyl-4-nitrophenyl)methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid methyl ester

Product 1

HCID 14403641(S)-5-diphenylacetyl-1-(3-methyl-4-nitrophenyl)methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid methyl esterYield 105.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Acetonitrile (16 ml) was added to a mixture of N,N'-dicyclohexylcarbodiimide (DCCI) (2.1080 g, 0.01022 mol), 1-hydroxybenzotriazole (HBTA) (1.3806 g, 0.01022 mol), and diphenylacetic acid (2.1685 g, 0.01022 mol), followed by stirring at room temperature for 20 minutes. A solution of (S)-1-(3-methyl-4-nitrophenyl)methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid methyl ester (VI-2) (2.7000 g, 0.00817 mol) in acetonitrile (14 ml) was added to the suspension, and the mixture was stirred at room temperature for 21 hours. An insoluble portion in the reaction mixture was filtered out and washed with acetonitrile, and then the filtrate and washings were joined and concentrated. The residue was dissolved in methylene chloride (40 ml), washed with a 10% sodium carbonate solution and a saturated brine, then dried over sodium sulfate and concentrated to obtain an orange oily material (4.5203 g). This crude oily material was purified by silica gel column chromatography (Kieselgel 60, 270 g, chloroform/methanol=60/11) to obtain the objective compound (V-2) (2.8250 g; yield: 65.9%) as colorless crystals (top: 174.5°-177° C.).

Workup

  1. stirringthe mixture was stirred at room temperature for 21 hours
  2. filtrationAn insoluble portion in the reaction mixture was filtered out
  3. washwashed with acetonitrile
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in methylene chloride (40 ml)
  6. washwashed with a 10% sodium carbonate solution
  7. dry with materiala saturated brine, then dried over sodium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-6cea3f30e7a94340a0738226bb8f42f8
Source dataset
uspto-grants-1995_03
Patent number
US05401736

Reaction notes

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