Formic Acid → HCID 57937462, compound

HRID 1435111Notes

Reaction equation

HRID 1435111 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[S:18][C:17]([C:19]([O:21][CH3:22])=[O:20])=[C:16]([O:23][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH:15]=3)=[C:9]([N+:31]([O-])=O)[CH:8]=2)[CH:4]=[N:3]1.[CH3:34]OC(OC)OC.C(O)=O>CO.[Zn]>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]3[N:13]([C:14]4[S:18][C:17]([C:19]([O:21][CH3:22])=[O:20])=[C:16]([O:23][CH2:24][C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[CH:15]=4)[CH:34]=[N:31][C:9]=3[CH:8]=2)[CH:4]=[N:3]1

Participants

6

Reactant 3

HCID 284Formic AcidHCID 9005Trimethyl orthoformateHCID 57937513HCID 57937513, compound

Product 1

HCID 57937462HCID 57937462, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

Methyl 5-{[4-(1-methyl-1H-pyrazol-4-yl)-2-nitrophenyl]amino}-3-[(phenylmethyl)oxy]-2-thiophenecarboxylate (1.0 g, 2.2 mmol) from a different batch than that made in Step A3, was dissolved In MeOH (30 mL). Trimethylorthoformate (6.0 mL, 54 mmol) was added followed by formic acid (0.81 ml, 21.5 mmol). Zinc dust (0.70 g, 11 mmol) was added and the reaction mixture was heated to 70° C. for 2 h and then cooled to rt. The reaction mixture was filtered through a pad of celite which was then washed with 20% MeOH/DCM. The crude reaction mixture was concentrated to remove the MeOH and the remaining mixture was poured into half-saturated aqueous NaHCO3 solution and then extracted with a mixture of 4:1 DCM:i-PrOH. The combined organics were dried over anhydrous MgSO4 and purified by flash chromatography to give 850 mg (89%) of the title compound, methyl 5-[5-(1-methyl-1H-pyrazol-4-yl)-1H-benzimidazol-1-yl]-3-[(phenylmethyl)oxy]-2-thiophenecarboxylate. MS (ESI): 445 [M+H]+

Workup

  1. temperaturecooled to rt
  2. filtrationThe reaction mixture was filtered through a pad of celite which
  3. washwas then washed with 20% MeOH/DCM
  4. customThe crude reaction mixture
  5. concentrationwas concentrated
  6. customto remove the MeOH
  7. additionthe remaining mixture was poured into half-saturated aqueous NaHCO3 solution
  8. extractionextracted with a mixture of 4:1 DCM
  9. dry with materialThe combined organics were dried over anhydrous MgSO4
  10. custompurified by flash chromatography

Sources & evidence

ORD record
ord-1068627244644454995e52b0a464482d
Source dataset
uspto-grants-2009_11
Patent number
US07615643B2

Reaction notes

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