Hydrochloric Acid → HCID 11965459, compound

HRID 1894042Notes

Reaction equation

HRID 1894042 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][C:5]([C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:16]=1[C:17]([F:20])([F:19])[F:18])[NH:13][C:12](=[O:21])[N:11]([NH:22][S:23]([CH3:26])(=[O:25])=[O:24])[C:10]2=[O:27])=[O:6].[BH4-].[Na+].Cl>CO.O>[OH:6][CH:5]([C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:16]=1[C:17]([F:18])([F:19])[F:20])[NH:13][C:12](=[O:21])[N:11]([NH:22][S:23]([CH3:26])(=[O:25])=[O:24])[C:10]2=[O:27])[CH2:4][CH2:3][O:2][CH3:1]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 59164408HCID 59164408, compound

Product 1

HCID 11965459HCID 11965459, compoundYield 94.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of N-[6-(3-methoxy-propionyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide (118 mg, 0.288 mmol) in MeOH (3 mL) at r.t. was treated with NaBH4 (77 mg, 2.03 mmol), added portionwise over a period of 3 h. After disappearance of the starting material, the reaction mixture was acidified with 2M aq HCl and diluted with water. The aqueous phase was extracted with EtOAc (2×), the organic phases were combined, washed with brine and dried (Na2SO4) and evaporated. The white powder obtained was purified by MPLC (RP-C18 column (particle size 5-21 μM) with CH3CN/water 1:2. The fractions containing the product were combined, the acetonitrile is distilled off and the residual water phase was extracted with EtOAc. The organic phase was washed with brine and dried (Na2SO4) and the solvent was removed in vacuo to provide the title compound (112 mg, 94%) as a white powder, mp 180-184° C. 1H-NMR (DMSO-d6, 400 MHz): 11.80 (br s, 1H), 10.35 (br s, 1H), 8.33 (s, 1H), 7.45 (s, 1H), 5.65 (d, J=6 Hz, 1H), 4.98-4.92 (m, 1H), 3.60-3.52 (m, 1H), 3.42-3.35 (m, 1H), 3.20 (s, 3H), 3.15 (s, 3H), 1.86-1.67 (m, 2H).

Workup

  1. additionadded portionwise over a period of 3 h
  2. extractionThe aqueous phase was extracted with EtOAc (2×)
  3. washwashed with brine
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customThe white powder obtained
  7. customwas purified by MPLC (RP-C18 column (particle size 5-21 μM) with CH3CN/water 1:2
  8. additionThe fractions containing the product
  9. distillationthe acetonitrile is distilled off
  10. extractionthe residual water phase was extracted with EtOAc
  11. washThe organic phase was washed with brine
  12. dry with materialdried (Na2SO4)
  13. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-97f02a06a8f344fca1b75b964eaab1b2
Source dataset
uspto-grants-2013_08
Patent number
US08513268B2

Reaction notes

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