Triethylamine → 4-[2-(4-tert-Butoxycarbonyl-piperazine-1-carbonyl)-4-cyano-phenyl]-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester

HRID 927013Notes

Reaction equation

HRID 927013 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]([C:25]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][C:26]=2[C:33](O)=[O:34])[N:8]([CH3:24])[C:9](=[O:23])[N:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[C:11]=1[CH3:12])=[O:5])[CH3:2].C(N(CC)CC)C.[N:43]1([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[CH:7]([C:25]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][C:26]=2[C:33]([N:46]2[CH2:47][CH2:48][N:43]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:44][CH2:45]2)=[O:34])[N:8]([CH3:24])[C:9](=[O:23])[N:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[C:11]=1[CH3:12])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 143452tert-Butyl piperazine-1-carboxylateHCID 1186916744-(2-Carboxy-4-cyano-phenyl)-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester2×

Product 1

HCID 1186916814-[2-(4-tert-Butoxycarbonyl-piperazine-1-carbonyl)-4-cyano-phenyl]-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

4-(2-carboxy-4-cyano-phenyl)-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester (intermediate 10)(30.0 mg, 0.06 mmol) is suspended in N,N-dimethylformamide (0.5 mL) and triethylamine (20.0 μL, 0.14 mmol) is added. The mixture is stirred at room temperature for 5 min and O-(7-azabonzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate (24.6 mg, 0.065 mmol) is added and the mixture is stirred for 15 min. A solution of tert-butyl 1-piperazinecaboxylate (17.2 mg, 0.09 mmol) in N,N-dimethylformamide (0.5 mL) and triethylamine (20.0 μL, 0.14 mmol) is added and the reaction mixture stirred at room temperature for 2 h. The crude product is purified by reversed phase HPLC. ESI mass spectrum [M-tBu+H]+=600; Retention time HPLC: 1.21 min (HPLC method Z018_S08).

Workup

  1. stirringthe mixture is stirred for 15 min
  2. stirringthe reaction mixture stirred at room temperature for 2 h
  3. customThe crude product is purified by reversed phase HPLC
  4. custom1.21 min (HPLC method Z018_S08)

Sources & evidence

ORD record
ord-ab69fe4600d8419cbb508be89b6d96f8
Source dataset
uspto-grants-2016_03
Patent number
US09290457B2

Reaction notes

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