Ethyl Acetate → HCID 21886609, compound

HRID 2216216Notes

Reaction equation

HRID 2216216 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]([O:11]C)OC)[N:3]=1.C(OC(=O)[NH:19][C:20]([C:22]1[S:23][C:24]([S:37][CH3:38])=[C:25]([S:27]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32](Br)[CH:31]=2)(=[O:29])=[O:28])[CH:26]=1)=[NH:21])(C)(C)C.C([O-])(O)=O.[Na+].CCOC(C)=O>C1COCC1.[Zn].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:8]([C:4]1[N:3]=[C:2]([C:32]2[CH:31]=[C:30]([S:27]([C:25]3[CH:26]=[C:22]([C:20]([NH2:21])=[NH:19])[S:23][C:24]=3[S:37][CH3:38])(=[O:29])=[O:28])[CH:35]=[CH:34][CH:33]=2)[CH:7]=[CH:6][CH:5]=1)=[O:11]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 218860672-Bromo-6-(dimethoxymethyl)pyridineHCID 145857672tert-butyl N-[4-(3-bromophenyl)sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 21886609HCID 21886609, compoundYield 95.8%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
65 °C

Procedure

To a slurry of Rieke Zinc (370 mg, 5.64 mmol) in THF (7.4 mL) was added a solution of 2-bromo-6-dimethoxymethyl-pyridine (400 mg, 1.7 mmol) in THF (2.6 mL). The suspension was heated to 65° C. for 2 h and the solution was filtered through a 0.23 μm syringe filter into a THF solution of {[4-(3-bromo-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester ((Example 27: step c) (250 mg, 0.5 mmol)) and Pd(PPh3)4 (0.112 mg, 0.1 mmol). The reaction was heated at 80° C. for 30 min, cooled, and was poured into aqueous NaHCO3. EtOAc (70 mL) was added and the layers were separated. The organic layer was washed with NH4Cl (2×20 mL), NaHCO3 (20 mL) and brine (30 mL) and was dried over sodium sulfate. Concentration of the solution followed by SiO2 flash column chromatography of the residue yielded 200 mg of the title compound which was contaminated with 2-dimethoxymethyl-pyridine. The material was treated with 1:1 TFA/DCM as described in Example 1: step d. Analogous purification by C18-HPLC yielded the title compound (118 mg, 38%) as a white solid. 1H-NMR (CD3OD) (aldehyde exists in hydrated form (acetal)) δ 8.60 (m, 2H), 8.44 (s, 1H), 8.33 (d, 1H, J=7.9), 8.27 (d, 1H, J=7.7), 8.23 (d, 1H, J=7.7), 8.12 (d, 1H, J=7.9), 7.9 (t, 1H, J=7.7), 5.82 (s, 1H), 2.74 (s, 3H). ESI-MS (m/z) (sample in MeOH): Calcd. for C18H15N3O3S3 (M+H): 418.0; found: 449.9 (MeOH adduct).

Workup

  1. filtrationthe solution was filtered through a 0.23 μm syringe
  2. temperatureThe reaction was heated at 80° C. for 30 min
  3. temperaturecooled
  4. customthe layers were separated
  5. washThe organic layer was washed with NH4Cl (2×20 mL), NaHCO3 (20 mL) and brine (30 mL)
  6. dry with materialwas dried over sodium sulfate

Sources & evidence

ORD record
ord-58b2e3009fca4dd885e8e95aa979bc2c
Source dataset
uspto-grants-2006_09
Patent number
US07109354B2

Reaction notes

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