Acetonitrile → 4-[(4S)-3-(cyanomethyl)-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidin-4-yl]-3-methylsulfonylbenzonitrile

HRID 927237Notes

Reaction equation

HRID 927237 reaction equation
[H-].[Na+].[O:3]=[C:4]1[N:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)[C:8]2[CH2:20][CH2:21][C:22](=[O:23])[C:7]=2[C@@H:6]([C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][C:25]=2[S:32]([CH3:35])(=[O:34])=[O:33])[NH:5]1.I[CH2:37][C:38]#[N:39].C(#N)C>O1CCCC1>[C:38]([CH2:37][N:5]1[C@H:6]([C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][C:25]=2[S:32]([CH3:35])(=[O:33])=[O:34])[C:7]2[C:22](=[O:23])[CH2:21][CH2:20][C:8]=2[N:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:17])[F:18])[CH:11]=2)[C:4]1=[O:3])#[N:39]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 24758Sodium hydrideHCID 69356Iodoacetonitrile3×HCID 77844826(S)-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]-pyrimidin-4-yl)-3-(methylsulfonyl)benzonitrile

Product 1

HCID 778448294-[(4S)-3-(cyanomethyl)-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidin-4-yl]-3-methylsulfonylbenzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% in mineral oil, 12 mg, 0.30 mmol) is added to a solution of (S)-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]-pyrimidin-4-yl)-3-(methylsulfonyl)benzonitrile (example 10A, 50 mg, 105 μmol) in tetrahydrofuran (3.0 mL). After 20 min, 2-iodoacetonitrile (8 μL, 0.11 mmol) is added. After 2 h, a second portion of 2-iodoacetonitrile (8 μL, 0.11 mmol) is added. After 2 h, a third portion of 2-iodoacetonitrile (8 μL, 0.11 mmol) is added. The mixture is stirred over night, treated with acetonitrile and purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 8 mg; ESI mass spectrum [M+H]+=515; Retention time HPLC: 1.01 min (Z018_504).

Workup

  1. waitAfter 2 h
  2. waitAfter 2 h
  3. custompurified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA)
  4. custom1.01 min (Z018_504)

Sources & evidence

ORD record
ord-785e8aa91c0f4fc689d6321a72db3266
Source dataset
uspto-grants-2016_03
Patent number
US09290459B1

Reaction notes

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