Triphosgene → N-(1-(4-cyanophenyl)-3,3-dimethyl-1-oxobutan-2-yl)-4-(6-methylpyridin-2-yl)piperazine-1-carboxamide

HRID 535780Notes

Reaction equation

HRID 535780 reaction equation
ClC(O[C:6](=[O:12])OC(Cl)(Cl)Cl)(Cl)Cl.Cl.[NH2:14][CH:15]([C:26]([CH3:29])([CH3:28])[CH3:27])[C:16]([C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=1)=[O:17].[CH3:30][C:31]1[N:36]=[C:35]([N:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[CH:34]=[CH:33][CH:32]=1>C(Cl)Cl>[C:22]([C:21]1[CH:24]=[CH:25][C:18]([C:16](=[O:17])[CH:15]([NH:14][C:6]([N:40]2[CH2:41][CH2:42][N:37]([C:35]3[CH:34]=[CH:33][CH:32]=[C:31]([CH3:30])[N:36]=3)[CH2:38][CH2:39]2)=[O:12])[C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:19][CH:20]=1)#[N:23]

Participants

5

Reactant 3

HCID 94429TriphosgeneHCID 27369461-(6-Methylpyridin-2-yl)piperazineHCID 682779744-(2-Amino-3,3-dimethylbutanoyl)benzonitrile hydrochloride

Product 1

HCID 56961883N-(1-(4-cyanophenyl)-3,3-dimethyl-1-oxobutan-2-yl)-4-(6-methylpyridin-2-yl)piperazine-1-carboxamideYield 90.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Bis(trichloromethyl)carbonate (60.6 mg, 0.20 mmol) was added portion-wise to 4-(2-amino-3,3-dimethylbutanoyl)benzonitrile hydrochloride (Example 3, 129 mg, 0.51 mmol) and TEA (0.285 mL, 2.04 mmol) in DCM (2 mL) under 1 minute at rt. After stirring for 20 min, a solution of 1-(6-methylpyridin-2-yl)piperazine (CAS 55745-89-6, 90 mg, 0.51 mmol) and TEA (0.142 mL, 1.02 mmol) in DCM (2 mL) was added drop-wise and the reaction was stirred for 90 min. The volatiles were removed before the reaction mixture was diluted with MeOH, filtered and purified by preparative HPLC. Fractions were pooled and freeze-dried to give N-(1-(4-cyanophenyl)-3,3-dimethyl-1-oxobutan-2-yl)-4-(6-methylpyridin-2-yl)piperazine-1-carboxamide (76 mg, 36%).

Workup

  1. stirringthe reaction was stirred for 90 min
  2. customThe volatiles were removed before the reaction mixture
  3. additionwas diluted with MeOH
  4. filtrationfiltered
  5. custompurified by preparative HPLC
  6. customfreeze-dried

Sources & evidence

ORD record
ord-b50ec146161044809f5c535770aa5008
Source dataset
uspto-grants-2014_10
Patent number
US08859556B2

Reaction notes

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