Diisopropylethylamine → (R)-4-(4-Cyanophenyl)-2,5-dioxo-N-(1,1-dioxo-hexahydro-1lambda6-thiopyran-4-yl)-1-(3-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidine-3(2H)-carboxamide

HRID 927256Notes

Reaction equation

HRID 927256 reaction equation
C(N(CC)C(C)C)(C)C.Cl[C:11](OC1C=CC([N+]([O-])=O)=CC=1)=[O:12].[O:23]=[C:24]1[N:29]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=2)[C:28]2[CH2:40][CH2:41][C:42](=[O:43])[C:27]=2[C@@H:26]([C:44]2[CH:51]=[CH:50][C:47]([C:48]#[N:49])=[CH:46][CH:45]=2)[NH:25]1.[O:52]=[S:53]1(=[O:60])[CH2:58][CH2:57][CH:56]([NH2:59])[CH2:55][CH2:54]1>CN(C)C1C=CN=CC=1.C(#N)C>[C:48]([C:47]1[CH:46]=[CH:45][C:44]([C@H:26]2[N:25]([C:11]([NH:59][CH:56]3[CH2:57][CH2:58][S:53](=[O:60])(=[O:52])[CH2:54][CH2:55]3)=[O:12])[C:24](=[O:23])[N:29]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:37])([F:38])[F:39])[CH:31]=3)[C:28]3[CH2:40][CH2:41][C:42](=[O:43])[C:27]2=3)=[CH:51][CH:50]=1)#[N:49]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 4188082H-Thiopyran-4-amine, tetrahydro-, 1,1-dioxideHCID 77844774(R)-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]-pyrimidin-4-yl)benzonitrile

Product 1

HCID 90311191(R)-4-(4-Cyanophenyl)-2,5-dioxo-N-(1,1-dioxo-hexahydro-1lambda6-thiopyran-4-yl)-1-(3-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidine-3(2H)-carboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

N,N-Diisopropylethylamine (137 μL, 0.81 mmol), 4-dimethylaminopyridine (27 mg, 0.22 mmol) and 4-nitrophenyl chloroformate (45 mg, 0.22 mmol) is added to a solution of (R)-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]-pyrimidin-4-yl)benzonitrile (example 1A, 80 mg, 0.20 mmol) in acetonitrile (2.0 mL), and the mixture is stirred at room temperature over night. 1,1-Dioxotetrahydro-2H-thiopyran-4-amine (74 mg, 0.40 mmol) is added, and the mixture is stirred for 1 h and purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 72 mg; ESI mass spectrum [M+H]+=573; Retention time HPLC: 1.01 min (Z018_S04).

Workup

  1. stirringthe mixture is stirred for 1 h
  2. custompurified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA)
  3. custom1.01 min (Z018_S04)

Sources & evidence

ORD record
ord-08e095c7a13f40a98bd7cb225505f020
Source dataset
uspto-grants-2016_03
Patent number
US09290459B1

Reaction notes

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