Acetic Acid → HCID 21358382, compound

HRID 1167831Notes

Reaction equation

HRID 1167831 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:8]2[S:9][CH:10]=[C:11]([C:13]3[CH:14]=[C:15]([NH:19][C:20]([C:22]4[S:23][C:24]([Cl:27])=[CH:25][CH:26]=4)=[O:21])[CH:16]=[CH:17][CH:18]=3)[N:12]=2)=[C:5]([NH2:7])[N:6]=1.C1([Li])C=CC=CC=1.[CH3:35][N:36]=[C:37]=[O:38].C(O)(=O)C>C1COCC1.CO.CN1CCCC1=O>[NH2:7][C:5]1[N:6]=[C:2]([NH:1][C:37]([NH:36][CH3:35])=[O:38])[S:3][C:4]=1[C:8]1[S:9][CH:10]=[C:11]([C:13]2[CH:14]=[C:15]([NH:19][C:20]([C:22]3[S:23][C:24]([Cl:27])=[CH:25][CH:26]=3)=[O:21])[CH:16]=[CH:17][CH:18]=2)[N:12]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 12228Methyl IsocyanateHCID 22994087HCID 22994087, compoundHCID 178506676HCID 178506676, compound2×

Product 1

HCID 21358382HCID 21358382, compoundYield 41%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of N-[3-(2′,4′-diamino-[2,5′]bithiazolyl-4-yl)phenyl]-5-chloro-thiophene-2-carboxamide (0.2307 mmol) (prepared as in Example E(3)), dissolved in anhydrous THF (5.0 mL) and anhydrous N-methylpyrolidinone (1.0 mL) at −78° C., was treated phenyllithium (0.2307 mmol), followed by methylisocyanate (0.3461 mmol). After 5 minutes a second portion of phenyllithium (0.2307 mmol) was added slowly. After stirring for an additional 15 minutes, the reaction was quenched with acetic acid (0.6921 mmol), and methanol (0.5 mL), concentrated, and purified by reverse phase HPLC. The major component was collected, dissolved in ethyl acetate, extracted with NaHCO3, brine, dried over MgSO4, concentrated until a precipitate formed, and filtered. Mass of the resulting light-yellow powder after drying under high vacuum was 46 mg (41% yield).

Workup

  1. concentrationconcentrated
  2. custompurified by reverse phase HPLC
  3. customThe major component was collected
  4. dissolutiondissolved in ethyl acetate
  5. extractionextracted with NaHCO3, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated until a precipitate
  8. customformed
  9. filtrationfiltered
  10. customMass of the resulting light-yellow powder after drying under high vacuum

Sources & evidence

ORD record
ord-122d1ecb0ac24d859cc2da5dfacf3d3e
Source dataset
uspto-grants-2003_09
Patent number
US06620828B2

Reaction notes

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