Acetic Acid → 3-Hydroxymethyl-4-[3-methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-benzonitrile

HRID 59664Notes

Reaction equation

HRID 59664 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH:12]2[C:21]3[C:20](=[O:22])[CH2:19][CH2:18][CH2:17][C:16]=3[N:15]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=3)[C:14](=[O:33])[N:13]2[CH3:34])=[C:7]([CH:11]=1)[C:8](O)=[O:9])#[N:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[BH4-].[Na+].C(O)(=O)C>C1COCC1.O>[OH:9][CH2:8][C:7]1[CH:11]=[C:3]([CH:4]=[CH:5][C:6]=1[CH:12]1[C:21]2[C:20](=[O:22])[CH2:19][CH2:18][CH2:17][C:16]=2[N:15]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:30])[F:31])[CH:24]=2)[C:14](=[O:33])[N:13]1[CH3:34])[C:1]#[N:2]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 682631,1'-CarbonyldiimidazoleHCID 4311764Sodium borohydrideHCID 1186921515-Cyano-2-[3-methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-benzoic acid2×

Product 1

HCID 1186928813-Hydroxymethyl-4-[3-methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-benzonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 5-cyano-2-[3-methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-benzoic acid (INTERMEDIATE 25, 710 mg, 1.51 mmol) in THF (11.2 mL) is added 1,1′-carbonyldiimidazole (270 mg, 1.66 mol) and the reaction mixture is stirred 90 min at room temp. The reaction mixture is cooled to 5° C. and a solution of sodium borohydride (85 mg, 2.27 mmol) in water (1.4 mL) is added dropwise. After stirring at room temp. for 3 h, the reaction mixture is acidified with dilute aqueous acetic acid, diluted with water and extracted with ethyl acetate. The organic phase is washed with water, dried over MgSO4 and concentrated under reduced pressure. The crude product is purified by reversed phase HPLC. Yield: 420 mg; ESI mass spectrum [M+H]+=456; Retention time HPLC: 0.62 min (X012_S02).

Workup

  1. temperatureThe reaction mixture is cooled to 5° C.
  2. stirringAfter stirring at room temp. for 3 h
  3. extractionextracted with ethyl acetate
  4. washThe organic phase is washed with water
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product is purified by reversed phase HPLC
  8. custom0.62 min (X012_S02)

Sources & evidence

ORD record
ord-b5398292f7ed4d67869b5a32594a6682
Source dataset
uspto-grants-2016_09
Patent number
US09440930B2

Reaction notes

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