Tetrahydrofuran → HCID 11574784, compound

HRID 2069191Notes

Reaction equation

HRID 2069191 reaction equation
C([SiH2][O:6][C:7](C)(C)[C:8]1[N:9]=[CH:10][N:11]([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][C:22]=2[N+:23]([O-:25])=[O:24])[NH:19][C:18](=[O:26])[N:17]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])[C:16]3=[O:32])[CH:12]=1)(C)(C)C.O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1.[NH4+].[OH-]>O.C(#N)C.O>[OH:6][CH2:7][C:8]1[N:9]=[CH:10][N:11]([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][C:22]=2[N+:23]([O-:25])=[O:24])[NH:19][C:18](=[O:26])[N:17]([NH:27][S:28]([CH3:31])(=[O:29])=[O:30])[C:16]3=[O:32])[CH:12]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 14923Ammonium HydroxideHCID 11726816Tetrabutylammonium Fluoride TrihydrateHCID 178455440HCID 178455440, compound

Product 1

HCID 11574784HCID 11574784, compoundYield 42.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
50 °C

Procedure

A mixture of 1 g (1.96 mmol) of N-{6-[4-(tert-butyl-dimethyl-silanyloxymethyl)-imidazol-1-yl]-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}-methanesulfonamide, 0.738 g (2.34 mmol) of tetrabutylammonium fluoride trihydrate and 20 ml of tetrahydrofuran is stirred at 50° C. for 18 hours. The reaction mixture is concentrated to dryness and the residue fractionated by medium pressure chromatography on a RP-C18 column (20 μM material) with acetonitril/water 1:1 (containing 0.1% trifluoroacetic acid) as eluent. The residue obtained by evaporation of fractions 2-5 is dissolved in water and the pH adjusted to ˜5 with diluted NH4OH solution. The product precipitates and is collected by filtration. The residue obtained from fractions 6-13 is fractionated by medium pressure chromatography on a RP-C18 column (20 μM material) with acetonitril/water 1:2 as eluent. During concentration of the fractions the product precipitates and is collected by filtration. Crystallization of all combined product fractions from DMSO/water gives 0.328 g of N-[6-(4-hydroxymethyl-imidazol-1-yl)-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide as a yellow powder, m.p. >300° C.

Workup

  1. concentrationThe reaction mixture is concentrated to dryness
  2. customThe residue obtained by evaporation of fractions 2-5
  3. customThe product precipitates
  4. filtrationis collected by filtration
  5. customThe residue obtained from fractions 6-13
  6. customDuring concentration of the fractions the product precipitates
  7. filtrationis collected by filtration
  8. customCrystallization of all combined product fractions from DMSO/water

Sources & evidence

ORD record
ord-0758ab1a8df64853bf329598c640cce7
Source dataset
uspto-grants-2012_10
Patent number
US08299085B2

Reaction notes

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