Formaldehyde → HCID 178448943, compound

HRID 23542Notes

Reaction equation

HRID 23542 reaction equation
[CH:1]1[CH:2]=[CH:3][C:4]2[N:9]=[C:8]([S+:10]([O-:18])[CH2:11][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][N:17]=3)[NH:7][C:5]=2[CH:6]=1.C=O.[CH3:21][C:22]([S:40][N:41]=[O:42])([CH3:39])[CH2:23][N:24]([CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:25]([CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[O:26].[CH:43]1(N=C=NC2CCCCC2)CCCCC1>C(#N)C>[N:17]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH2:11][S:10]([C:8]1[NH:7][C:5]2[C:6]([CH2:43][O:30][C:29](=[O:31])[CH2:28][CH2:27][C:25](=[O:26])[N:24]([CH2:23][C:22]([CH3:21])([S:40][N:41]=[O:42])[CH3:39])[CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:1][CH:2]=[CH:3][C:4]=2[N:9]=1)=[O:18]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 10868DicyclohexylcarbodiimideHCID 102367173-{N-[2-Methyl-2-(nitrosothio)propyl)-N-benzylcarbamoyl]propanoic acidHCID 178527210HCID 178527210, compound

Product 1

HCID 178448943HCID 178448943, compoundYield 55.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of timoprazole (0.51 g, 1.98 mmol) and 37% formaldehyde (0.80 ml) in acetonitrile (5 ml) was heated at 70° C. for 15 min. The reaction was evaporated to give a solid that was washed twice with ethyl ether/ethyl acetate (4:1) and dissolved in dichloromethane (10 ml). To this solution was added Example 1c (0.65 g, 2 mol), 4-(N—N-dimethylamino)pyridine (10 mg) and dicyclohexylcarbodiimide (1M in dichloromethane, 4 ml, 4 mmol). After stirring at room temperature for 3 hours, the reaction was concentrated under vacuum and the residue was purified by flash column chromatography (ethyl acetate/hexane, 4:1 to 7:1) to afford the title compound (0.65 g, 54.7%) as a green foam. 1H NMR (300 MHz, CDCl3): δ1.82 and 1.91 (2 s, 6H), 2.63 and 2.75 (2br s, 4H), 4.08 and 4.13 (2 s, 2H), 4.70 and 4.85 (2 s, 2H), 4.88 (d, J=14 Hz, 1H), 4.92 (d, J=14 Hz, 1H), 6.36 (d, J=11.4 Hz, 1H), 6.42 (d, =11.4 Hz, 1H), 7.00 and 7.06 (2 d, J=6.8 Hz, 2H), 7.207.64 (m, 9H), 7.81 (d, !=7.7 Hz, 1H), 8.54 (d, J=4 Hz, 1H); 13C NMR (75 MHz, CDCl): δ 27.29, 27.94, 28.88, 52.58, 55.29, 58.18, 62.22, 65.04, 110.73, 120.73, 122.97, 123.85, 125.21, 125.30, 125.58, 127.41, 128.76, 135.03, 135.79, 136.66, 141.70, 149.71, 150.20, 151.66, 171.80, 172.76; LCMS (m/e): 594 (M+1).

Workup

  1. customThe reaction was evaporated
  2. customto give a solid
  3. washthat was washed twice with ethyl ether/ethyl acetate (4:1)
  4. dissolutiondissolved in dichloromethane (10 ml)
  5. concentrationthe reaction was concentrated under vacuum
  6. customthe residue was purified by flash column chromatography (ethyl acetate/hexane, 4:1 to 7:1)

Sources & evidence

ORD record
ord-0c06ab515e3e4b1aa61f1fc91a3116db
Source dataset
uspto-grants-2005_02
Patent number
US06852739B1

Reaction notes

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