Potassium Carbonate → HCID 11464439, compound

HRID 1160115Notes

Reaction equation

HRID 1160115 reaction equation
Br[CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=2)[C:3]1=[O:17].[NH2:18][C:19]1[N:24]=[C:23]([SH:25])[C:22]([C:26]#[N:27])=[C:21]([S:28][CH3:29])[N:20]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[NH2:18][C:19]1[N:20]=[C:21]([S:28][CH3:29])[C:22]([C:26]#[N:27])=[C:23]([S:25][CH:2]2[CH2:6][CH2:5][N:4]([C:7]3[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=3)[C:3]2=[O:17])[N:24]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2780456HCID 2780456, compoundHCID 178503513HCID 178503513, compound

Product 1

HCID 11464439HCID 11464439, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a round-bottomed flask was added 3-bromo-1-[3-(trifluoromethyl)-phenyl]-pyrrolidin-2-one (21) (308 mg, 1.0 mmol, 1.0 eq.), DMF (3.0 mL), 2-amino-4-mercapto-6-methylsulfanyl-pyrimidine-5-carbonitrile (198 mg, 1.0 mmol, 1.0 eq.), and potassium carbonate (207 mg, 1.5 mmol, 1.5 eq.). The reaction was stirred at RT overnight before quenching with H2O (10 mL) and EtOAc (50 mL). The EtOAc layer washed with 10% LiCl (20 mL, 2×), washed with brine, dried with Na2SO4, and concentrated to give crude product. Pure 2-amino-4-methylsulfanyl-6-[2-oxo-1-(3-trifluoromethyl-phenyl)-pyrrolidin-3-ylsulfanyl]-pyrimidine-5-carbonitrile was precipitated out with 20:80 EtOAc:Hexanes, filtered, and dried under high vacuum (193 mg, 45%). LC/MSD (HP Series 1100 MSD): Expected MW: 425, Observed M+H, 426.1, Retention time: 1.60 min. ANALYTICAL HPLC: >98%, Retention time: 5.56 min (8 minute run). 1H-NMR (d6-DMSO): 8.20 (s, 1 H), 7.85 (d, 1H), 7.69 (t, 1H), 7.50 (d, 1H), 4.75 (t, 1H), 4.00 (dt, 2H), 2.72 (m, 1H), 2.40 (s, 3H), 2.39 (m, 1H) ppm.

Workup

  1. custombefore quenching with H2O (10 mL) and EtOAc (50 mL)
  2. washThe EtOAc layer washed with 10% LiCl (20 mL, 2×)
  3. washwashed with brine
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated
  6. customto give crude product
  7. customPure 2-amino-4-methylsulfanyl-6-[2-oxo-1-(3-trifluoromethyl-phenyl)-pyrrolidin-3-ylsulfanyl]-pyrimidine-5-carbonitrile was precipitated out with 20:80 EtOAc
  8. filtrationHexanes, filtered
  9. customdried under high vacuum (193 mg, 45%)
  10. custom>98%, Retention time: 5.56 min (8 minute run)

Sources & evidence

ORD record
ord-a139222b32fe41bb8716419561e15bf7
Source dataset
uspto-grants-2010_10
Patent number
US07816353B2

Reaction notes

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