Acetic Acid → HCID 178521694, compound

HRID 1805295Notes

Reaction equation

HRID 1805295 reaction equation
C(O)(=O)C.[NH2:5][C:6]1[CH:7]=[N:8][CH:9]=[CH:10][C:11]=1[NH:12][C:13]([C:15]1([NH:18][C:19](=[O:28])[O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:17][CH2:16]1)=O.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl.CO>[NH:12]1[C:11]2[CH:10]=[CH:9][N:8]=[CH:7][C:6]=2[N:5]=[C:13]1[C:15]1([NH:18][C:19](=[O:28])[O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:17][CH2:16]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 66605329HCID 66605329, compound

Product 1

HCID 178521694HCID 178521694, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
120 °C

Procedure

To a medium size microwave vial was added 5 mL of acetic acid and 850 mgs of the crude reaction mixture prepared in the previous step (benzyl 1-(4-aminopyridin-3-lcarbamoyl)cyclopropylcarbamate and benzyl 1-(3-aminopyridin-4-ylcarbamoyl)cyclopropylcarbamate). The vial was sealed and the mixture heated at 120° C. for 70 minutes in the microwave. The vessel was cooled to near 0° C. and 50 mL of cold saturated sodium carbonate was added along with 100 mL of 10:1 DCM/methanol. The product was extracted; the organics washed with brine, dried over magnesium sulfate and evaporated. The product mixture was taken up in 15 mL of methanol and purified using a Shimadzu preparative HPLC employing methanol/water/trifluoroacetic acid where solvent A was 10% methanol/90% water/0.1% trifluoroacetic acid and solvent B was 10% water/90% methanol/0.1% trifluoroacetic acid with a Phenomenex-Luna 10 μm C18 30×100 mm column at a gradient of 0-100% B and a flow rate of 40 mL/min. over 15 minutes with a 10 minute hold. Solvent was removed giving a 70% yield of benzyl 1-(1H-imidazo[4,5-c]pyridin-2-yl)cyclopropylcarbamate as a light yellow solid. 1H NMR (400 MHz, CD3OD) δ ppm 1.44-1.59 (m, 2 H), 1.68-1.83 (m, 2 H), 5.05-5.14 (m, 2 H), 6.99-7.14 (m, 1 H), 7.19-7.41 (m, 4 H), 7.88-7.97 (m, 1 H), 8.40 (d, J=6.5 Hz, 1 H), 8.97 (s, 1H). LCMS rt=1.483 min., m/z 309.2 (M+H), 94.5% purity.

Workup

  1. customreaction mixture
  2. customThe vial was sealed
  3. temperatureThe vessel was cooled to near 0° C.
  4. extractionThe product was extracted
  5. washthe organics washed with brine
  6. dry with materialdried over magnesium sulfate
  7. customevaporated
  8. custompurified
  9. customSolvent was removed

Sources & evidence

ORD record
ord-fc0ab41dde9c4f1790b29f96aa4774d8
Source dataset
uspto-grants-2013_01
Patent number
US08354410B2

Reaction notes

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