Water → Methyl 4-(4-Cyanophenyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidine-3(2H)-carboxylate

HRID 927221Notes

Reaction equation

HRID 927221 reaction equation
[O:1]=[C:2]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[C:6]2[CH2:18][CH2:19][C:20](=[O:21])[C:5]=2[CH:4]([C:22]2[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=2)[NH:3]1.[H-].[Na+].Cl[C:33]([O:35][CH3:36])=[O:34].O>O1CCCC1>[C:26]([C:25]1[CH:24]=[CH:23][C:22]([CH:4]2[N:3]([C:33]([O:35][CH3:36])=[O:34])[C:2](=[O:1])[N:7]([C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:15])([F:16])[F:17])[CH:9]=3)[C:6]3[CH2:18][CH2:19][C:20](=[O:21])[C:5]2=3)=[CH:29][CH:28]=1)#[N:27]

Participants

6

Reactant 4

HCID 962WaterHCID 6586Methyl chloroformateHCID 24758Sodium hydrideHCID 778447734-(2,5-Dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]-pyrimidin-4-yl)benzonitrile

Product 1

HCID 90311121Methyl 4-(4-Cyanophenyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidine-3(2H)-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]pyrimidin-4-yl)benzonitrile (example 1, 30 mg, 0.076 mmol) in tetrahydrofuran (0.5 mL) is added to a suspension of sodium hydride (60% in mineral oil, 4 mg, 0.1 mmol) in dry tetrahydrofuran. After 20 min methyl chloroformate (6 μL, 0.078 mmol) is added, and the mixture is stirred at room temperature for 1 h. Water is added and the mixture is a) extracted with dichloromethane. The combined organic layers are concentrated, and the residue is purified by reversed phase HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% NH3). Yield: 2 mg; ESI mass spectrum [M+H]+=456; Retention time HPLC: 1.10 min (V011_S01).

Workup

  1. extractionextracted with dichloromethane
  2. concentrationThe combined organic layers are concentrated
  3. customthe residue is purified by reversed phase HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% NH3)
  4. custom1.10 min (V011_S01)

Sources & evidence

ORD record
ord-1e8cc281a8c444e68d639f67f2ba1473
Source dataset
uspto-grants-2016_03
Patent number
US09290459B1

Reaction notes

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