Diisopropylethylamine → 1,3,7,8-Tetrahydro-8-[[[(4-Methylphenyl)Sulfonyl]Oxy]Methyl]-2H-[1,4]Dioxino[2,3-e]Benzimidazol-2-One

HRID 982678Notes

Reaction equation

HRID 982678 reaction equation
Cl.Cl.[CH3:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([O:13][CH2:14][C@@H:15]2[O:20][C:19]3[C:21]([NH2:26])=[C:22]([NH2:25])[CH:23]=[CH:24][C:18]=3[O:17][CH2:16]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1.[C:27](C1NC=CN=1)(C1NC=CN=1)=[O:28].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH3:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([O:13][CH2:14][CH:15]2[O:20][C:19]3[C:21]4[NH:26][C:27](=[O:28])[NH:25][C:22]=4[CH:23]=[CH:24][C:18]=3[O:17][CH2:16]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 86586513[(2R)-7,8-diamino-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate dihydrochloride

Product 1

HCID 102929161,3,7,8-Tetrahydro-8-[[[(4-Methylphenyl)Sulfonyl]Oxy]Methyl]-2H-[1,4]Dioxino[2,3-e]Benzimidazol-2-One

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 0.30 g (0.71 mmole) of [(2R)-7,8-diamino-2,3-dihydro-1,4 benzodioxin-2-yl]methyl 4-methylbenzenesulfonate dihydrochloride in 50 mL of methylene chloride was added 0.50 g (3.0 mmole) of carbonyl diimidazole and 0.65 g (5.0 mmole) of diisopropylethylamine. The reaction mixture was stirred under nitrogen for 15 hours. The mixture was then concentrated in vacuum and 250 mL of ethyl acetate added. This solution was washed with 250 mL portions each of 2 N aqueous HCl, saturated aqueous sodium bicarbonate and saturated brine, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was column chromatographed on 25 g of silica gel, using a gradient elution commencing with chloroform and ending with 3% methanol in chloroform. The product fractions were combined and evaporated in vacuum to give 0.21 g of the (R)-enantiomer of the title compound as an off-white solid, m.p. 202-204° C.

Workup

  1. concentrationThe mixture was then concentrated in vacuum and 250 mL of ethyl acetate
  2. additionadded
  3. washThis solution was washed with 250 mL portions each of 2 N aqueous HCl, saturated aqueous sodium bicarbonate and saturated brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuum
  7. customchromatographed on 25 g of silica gel
  8. customevaporated in vacuum

Sources & evidence

ORD record
ord-bb2d7e9e9298490f94fa8d872f12e7c3
Source dataset
uspto-grants-2005_03
Patent number
US06861434B2

Reaction notes

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