Methanol → N-[6-(1-hydroxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide

HRID 1894010Notes

Reaction equation

HRID 1894010 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[C:14]([F:17])([F:16])[F:15])[NH:10][C:9](=[O:18])[N:8]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])[C:7]2=[O:24])(=[O:3])[CH3:2].CO.[BH4-].[Na+]>C1COCC1>[OH:3][CH:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[C:14]([F:16])([F:15])[F:17])[NH:10][C:9](=[O:18])[N:8]([NH:19][S:20]([CH3:23])(=[O:21])=[O:22])[C:7]2=[O:24])[CH3:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 11965693HCID 11965693, compound

Product 1

HCID 11965295N-[6-(1-hydroxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamideYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of N-(6-acetyl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulfonamide (12.1 g, 33.1 mmol) in THF (150 mL)/MeOH (150 mL) under nitrogen was treated with sodium borohydride (25.0 g, 660 mmol) portionwise over 18 h at r.t. The suspension was then poured into a mixture of ice/concentrated EtOAc. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica gel 60, DCM/MeOH 9:1) affording colorless crystals, which were recrystallized in EtOAc to provide N-[6-(1-hydroxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide (8.85 g, 24.1 mmol, 73%) as a white powder, m.p. 263-268° C., 1H-NMR (DMSO-d6, 400 MHz) 8.41 (s, 1H), 7.49 (s, 1H), 5.66 (m, 1 H), 5.03 (br s, 1 H), 3.18 (s, 3H), 1.36 (d, J=6.2 Hz, 3 H).

Workup

  1. additionThe suspension was then poured into a mixture of ice/concentrated EtOAc
  2. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography (silica gel 60, DCM/MeOH 9:1)
  6. customaffording colorless crystals, which
  7. customwere recrystallized in EtOAc

Sources & evidence

ORD record
ord-44dd542a4638437e83d801ae443028d6
Source dataset
uspto-grants-2013_08
Patent number
US08513268B2

Reaction notes

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