Diisopropylethylamine → HCID 136603191, compound

HRID 1022946Notes

Reaction equation

HRID 1022946 reaction equation
[NH2:1][C:2]1[CH:6]=[C:5]([Br:7])[S:4][C:3]=1[C:8]([NH2:10])=[O:9].Cl[C:12]([C:14]12[N:20]([C:21]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:22])[CH:17]([CH2:18][CH2:19]1)[CH2:16][CH2:15]2)=O.C(N(C(C)C)C(C)C)C.C(=O)([O-])O.[Na+]>O1CCCC1>[Br:7][C:5]1[S:4][C:3]2[C:8](=[O:9])[NH:10][C:12]([C:14]34[N:20]([C:21]([O:23][CH2:24][C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)=[O:22])[CH:17]([CH2:16][CH2:15]3)[CH2:18][CH2:19]4)=[N:1][C:2]=2[CH:6]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 10517849HCID 10517849, compoundHCID 219758623-Amino-5-bromothiophene-2-carboxamide

Product 1

HCID 136603191HCID 136603191, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 3-amino-5-bromothiophene-2-carboxamide (221 mg) produced in Example 1, step D, the crude product (2.0 mmol) of benzyl 1-(chlorocarbonyl)-7-azabicyclo[2.2.1]heptane-7-carboxylate produced above and tetrahydrofuran (10 mL) was added N-ethyl-N-(1-methylethyl)propan-2-amine (0.70 mL) at room temperature. After stirring for 1 hr, the reaction system was poured into saturated aqueous sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To the residue were added ethanol (10 mL) and 2M sodium hydroxide (2.5 mL), and the mixture was stirred at 100° C. overnight. The reaction system was cooled to room temperature, poured into saturated aqueous sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate/hexane and methanol/ethyl acetate) to give the title compound (313 mg) as a white solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialThe extract was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. additionTo the residue were added ethanol (10 mL) and 2M sodium hydroxide (2.5 mL)
  5. stirringthe mixture was stirred at 100° C. overnight
  6. additionpoured into saturated aqueous sodium hydrogen carbonate
  7. extractionthe mixture was extracted with ethyl acetate
  8. dry with materialThe extract was dried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by basic silica gel column chromatography (ethyl acetate/hexane and methanol/ethyl acetate)

Sources & evidence

ORD record
ord-b59c090849fe4d648c4f92afc03ab1f1
Source dataset
uspto-grants-2014_05
Patent number
US08722660B2

Reaction notes

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