Triethylamine → 4-{2-[5-Acetyl-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidin-4-yl]-5-cyano-benzoylamino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 927012Notes

Reaction equation

HRID 927012 reaction equation
[C:1]([C:4]1[CH:5]([C:23]2[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][C:24]=2[C:25]([OH:27])=O)[N:6]([CH3:22])[C:7](=[O:21])[N:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[C:9]=1[CH3:10])(=[O:3])[CH3:2].[N:34]1([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:39][CH2:38]N[CH2:36][CH2:35]1.[CH2:47]([N:49](CC)CC)C>CN(C)C=O>[C:43]([O:42][C:40]([N:34]1[CH2:35][CH2:36][CH:47]([NH:49][C:25](=[O:27])[C:24]2[CH:28]=[C:29]([C:32]#[N:33])[CH:30]=[CH:31][C:23]=2[CH:5]2[C:4]([C:1](=[O:3])[CH3:2])=[C:9]([CH3:10])[N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=3)[C:7](=[O:21])[N:6]2[CH3:22])[CH2:38][CH2:39]1)=[O:41])([CH3:44])([CH3:45])[CH3:46]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 118691679US9290457, Intermediate 62×

Product 1

HCID 1186916904-{2-[5-Acetyl-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidin-4-yl]-5-cyano-benzoylamino}-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 2-[5-acetyl-3,6-dimethyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidin-4-yl]-5-cyano-benzoic acid (intermediate 6, 40.0 mg, 0.09 mmol) in N,N-dimethylformamide (1 mL) triethylamine (25.0 μL, 0.18 mmol) is added and stirred at room temperature for 5 min. Then O-(7-azabonzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate (34.9 mg, 0.09 mmol) is added and stirred for 15 min. A solution of tert-butyl 1-piperazinecarboxylate (24.4 mg, 0.13 mmol) and triethylamine (25.0 μL, 0.18 mmol) in N,N-dimethylformamide (1 mL) is added and stirred at room temperature for 72 h. The reaction mixture is purified by reversed phase HPLC. ESI mass spectrum [M-Boc+H]+=526; Retention time HPLC: 1.16 min (HPLC method Z018_S04).

Workup

  1. stirringstirred for 15 min
  2. stirringstirred at room temperature for 72 h
  3. customThe reaction mixture is purified by reversed phase HPLC
  4. custom1.16 min (HPLC method Z018_S04)

Sources & evidence

ORD record
ord-2330a4cd6e074a079073d867ee8dcf81
Source dataset
uspto-grants-2016_03
Patent number
US09290457B2

Reaction notes

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