Water → 4-Nitrophenyl 4-(4-Cyanophenyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,5,6,7,8-hexahydroquinazoline-3(4H)-carboxylate

HRID 517206Notes

Reaction equation

HRID 517206 reaction equation
C(N(CC)C(C)C)(C)C.[O:10]=[C:11]1[NH:20][CH:19]([C:21]2[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=2)[C:18]2[C:17](=[O:29])[CH2:16][CH2:15][CH2:14][C:13]=2[N:12]1[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=1.Cl[C:41]([O:43][C:44]1[CH:49]=[CH:48][C:47]([N+:50]([O-:52])=[O:51])=[CH:46][CH:45]=1)=[O:42].O>CN(C)C1C=CN=CC=1.ClCCl>[C:25]([C:24]1[CH:23]=[CH:22][C:21]([CH:19]2[C:18]3[C:17](=[O:29])[CH2:16][CH2:15][CH2:14][C:13]=3[N:12]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:37])[F:38])[CH:31]=3)[C:11](=[O:10])[N:20]2[C:41]([O:43][C:44]2[CH:45]=[CH:46][C:47]([N+:50]([O-:52])=[O:51])=[CH:48][CH:49]=2)=[O:42])=[CH:28][CH:27]=1)#[N:26]

Participants

7

Reactant 4

HCID 962WaterHCID 81531Diisopropylethylamine2×HCID 821294-Nitrophenyl chloroformate2×HCID 86732326HCID 86732326, compound

Product 1

HCID 867323254-Nitrophenyl 4-(4-Cyanophenyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,5,6,7,8-hexahydroquinazoline-3(4H)-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

N,N-Diisopropylethylamine (1.65 mL, 9.72 mmol) and 4-dimethylaminopyridine (59 mg, 0.49 mmol) are added to a solution of 4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-benzonitrile (example 1, 1.00 g, 2.43 mmol) in dichloromethane (6 mL), and the mixture is cooled in an ice bath. A solution of 4-nitrophenyl chloroformate (540 mg, 2.67 mmol) in dichloromethane (2 mL) is added, and the mixture is warmed to room temperature. After 3 h another portion of 4-nitrophenyl chloroformate (980 mg, 4.86 mmol) and N,N-diisopropylethylamine (830 μL, 4.86 mmol) are added, and the mixture is stirred over night. Water is added and the mixture is extracted twice with dichloromethane. The combined organic layers are dried over Na2SO4 and concentrated under reduced pressure. The residue is purified twice by flash chromatography on silica (first purification: gradient cyclohexane/ethyl acetate 100:0 to 70:30, second purification: gradient cyclohexane/ethyl acetate 100:0 to 50:50). Yield: 374 mg; ESI mass spectrum [M+H]+=577, Retention time HPLC: 0.92 min (Z018_S04).

Workup

  1. temperaturethe mixture is cooled in an ice bath
  2. extractionthe mixture is extracted twice with dichloromethane
  3. dry with materialThe combined organic layers are dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is purified twice by flash chromatography on silica (first purification: gradient cyclohexane/ethyl acetate 100:0 to 70:30, second purification: gradient cyclohexane/ethyl acetate 100:0 to 50:50)
  6. custom0.92 min (Z018_S04)

Sources & evidence

ORD record
ord-941a7ac57d874f6f99665441d289211d
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

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