Benzimidazole → Pantoprazole

HRID 2245616Notes

Reaction equation

HRID 2245616 reaction equation
[F:1][CH:2]([F:25])[O:3][C:4]1[CH:24]=[CH:23][C:7]2[NH:8][C:9]([S:11][CH2:12][C:13]3[C:18]([O:19][CH3:20])=[C:17]([O:21][CH3:22])[CH:16]=[CH:15][N:14]=3)=[N:10][C:6]=2[CH:5]=1.N1C2C=CC=CC=2NC=1.[O-]Cl.[Na+].[OH-].[Na+].S(S([O-])=O)([O-])(=O)=[O:41].[Na+].[Na+]>O1CCCC1.C(#N)C.O.C(O)(C)C.C(O)C.CO>[CH3:22][O:21][C:17]1[CH:16]=[CH:15][N:14]=[C:13]([CH2:12][S+:11]([O-:41])[C:9]2[NH:8][C:7]3[CH:23]=[CH:24][C:4]([O:3][CH:2]([F:1])[F:25])=[CH:5][C:6]=3[N:10]=2)[C:18]=1[O:19][CH3:20]

Participants

12

Reactant 5

HCID 5798Benzimidazole3×HCID 14798Sodium Hydroxide2×HCID 656671Sodium PyrosulfiteHCID 9799341Pantoprazole sulfideHCID 23665760Sodium Hypochlorite2×

Product 1

HCID 178493214Pantoprazole

Reagents, catalysts & solvents 6

HCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 3776IsopropanolSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

Chlorinated pantoprazole derivatives IV and V can be produced by reaction of 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl) methyl]thio]-1H-benzimidazole with NaOH and about 3 to about 5 molar equivalents of NaOCl under conditions especially developed to produce these derivatives. Those conditions include admixing 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl) methyl]thio]-1H-benzimidazole compound VI with a quantity of NaOCl of about 3 to about 5, preferably about 1.5 to about 2.5 molar equivalents and a quantity of NaOH of about 1.5 to about 2.5 molar equivalents. Preferred relative quantities of these reagents are about 1.8 molar equivalents of each with respect to benzimidazole VI. Compound VI, NaOCl and NaOH are admixed in a water miscible protic solvent, such as methanol, ethanol and i-propanol, or water miscible aprotic solvent such as acetonitrile and tetrahydrofuran. The reaction is conducted at ambient or elevated temperature, preferably ambient temperature. In all other respects, the reaction conditions can be the same as those of the process previously described for oxidizing 2-[(pyridinyl)methyl]thio-substituted benzimidazoles selectively to 2-[(pyridinyl)methyl]sulfinyl-substituted benzimidazoles. After completing the reaction, the mixture is treated with aqueous sodium metabisulfite to pH 8.5 and stirred at room temperature for 1 hour. The two phases from the resulting reaction are separated, and the solvent is evaporated with vacuum. Isolation of compounds IV and V can be performed by chromatography. Compounds IV and V will be produced in mixture with pantoprazole. In fact, pantoprazole may be the major product.

Workup

  1. customto produce these derivatives
  2. customelevated temperature, preferably ambient temperature
  3. customIn all other respects, the reaction conditions
  4. customthe reaction
  5. customThe two phases from the resulting reaction
  6. customare separated
  7. customthe solvent is evaporated with vacuum

Sources & evidence

ORD record
ord-73b9959bb51d4e008bf79fb5ead4a505
Source dataset
uspto-grants-2010_03
Patent number
US07683177B2

Reaction notes

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