Methylamine → 4-(4-Cyano-2-fluorophenyl)-N-methyl-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidine-3(2H)-carboxamide

HRID 927257Notes

Reaction equation

HRID 927257 reaction equation
ClC(OC1C=CC([N+]([O-])=O)=CC=1)=[O:3].[O:14]=[C:15]1[N:20]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=2)[C:19]2[CH2:31][CH2:32][C:33](=[O:34])[C:18]=2[CH:17]([C:35]2[CH:42]=[CH:41][C:38]([C:39]#[N:40])=[CH:37][C:36]=2[F:43])[NH:16]1.[CH:44]([N:47]([CH2:51]C)C(C)C)(C)C.CN>CN(C)C1C=CN=CC=1.C(#N)C>[C:39]([C:38]1[CH:41]=[CH:42][C:35]([CH:17]2[N:16]([C:51]([NH:47][CH3:44])=[O:3])[C:15](=[O:14])[N:20]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:29])[F:30])[CH:22]=3)[C:19]3[CH2:31][CH2:32][C:33](=[O:34])[C:18]2=3)=[C:36]([F:43])[CH:37]=1)#[N:40]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformate2×HCID 903110934-(2,5-Dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]-pyrimidin-4-yl)-3-fluorobenzonitrile

Product 1

HCID 903107184-(4-Cyano-2-fluorophenyl)-N-methyl-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidine-3(2H)-carboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6342AcetonitrileSolvent

Procedure

4-Nitrophenyl chloroformate (23 mg, 0.11 mmol) is added to a solution of 4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]pyrimidin-4-yl)-3-fluorobenzonitrile (example 18, 43 mg, 0.10 mmol), N,N-diisopropylethylamine (70 μL, 0.41 mmol) and 4-dimethylaminopyridine (14 mg, 0.11 mmol) in acetonitrile (3.0 mL), and the mixture is stirred at room temperature over night. Another portion of 4-Nitrophenyl chloroformate (50 mg, 0.24 mmol) and 4-dimethylaminopyridine (30 mg, 0.24 mmol) is added, and the mixture is stirred over night. Methylamine (2.0 M in tetrahydrofuran, 155 μL, 0.31 mmol) is added, and the mixture is stirred for 20 min at room temperature and purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 27 mg; ESI mass spectrum [M+H]+=473; Retention time HPLC: 0.59 min (001_CA07).

Workup

  1. stirringthe mixture is stirred over night
  2. stirringthe mixture is stirred for 20 min at room temperature
  3. custompurified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA)
  4. custom0.59 min (001_CA07)

Sources & evidence

ORD record
ord-72265c117de74d9e92c625da179bd63a
Source dataset
uspto-grants-2016_03
Patent number
US09290459B1

Reaction notes

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