Isopropyl iodide → HCID 10278818, compound

HRID 131577Notes

Reaction equation

HRID 131577 reaction equation
I[CH:2]([CH3:4])[CH3:3].C(=O)([O-])[O-].[K+].[K+].[CH3:11][C:12]1[C:16]([CH2:17][C:18]2[S:33][C:21]3[N:22]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:23](=[O:28])[N:24]([CH3:27])[C:25](=[O:26])[C:20]=3[C:19]=2[C:34]([N:36]2[CH2:40][C@H:39]([OH:41])[CH2:38][O:37]2)=[O:35])=[C:15]([CH3:42])[NH:14][N:13]=1>CN(C)C=O.O>[OH:41][C@@H:39]1[CH2:38][O:37][N:36]([C:34]([C:19]2[C:20]3[C:25](=[O:26])[N:24]([CH3:27])[C:23](=[O:28])[N:22]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:21]=3[S:33][C:18]=2[CH2:17][C:16]2[C:15]([CH3:42])=[N:14][N:13]([CH:2]([CH3:4])[CH3:3])[C:12]=2[CH3:11])=[O:35])[CH2:40]1

Participants

6

Reactant 3

HCID 6362Isopropyl iodide2×HCID 11430Potassium Carbonate2×HCID 10226546AR-C155858

Product 1

HCID 10278818HCID 10278818, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

2-Iodopropane (0.1 ml) and potassium carbonate (100 mg) were added to a solution of 6-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-5-[(4S)-4-hydroxyisoxazolidin-2-ylcarbonyl]-1-(isobutyl)-3-methylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (example 11, 100 mg) in dimethylformamide (1 ml) and the mixture stirred at 100° C. After 2 hours, further 2-iodopropane (0.2 ml) and potassium carbonate (200 mg) were added. After a further 16 hours, the mixture was cooled to room temperature, diluted with water (20 ml) and extracted with ethyl acetate (2×20 ml). Combined organic extracts were treated with pyrrolidine (0.1 ml) and after 1 hour were dried over anhydrous magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified by reverse-phase HPLC with gradient 0.1% aqueous ammonium acetate/acetonitrile elution to give the title compound (58 mg) as a foam. MS (APCI) 504 [M+H]+. δ 1HDMSO 0.87 (6H, d), 1.31 (6H, d), 1.99-2.14 (7H, m), 3.19-3.21 (3H, m), 3.45-4.13 (8H, m), 4.40 (1H, sept), 4.56-4.79 (1H, m), 5.48-5.55 (1H, m).

Workup

  1. waitAfter a further 16 hours
  2. temperaturethe mixture was cooled to room temperature
  3. extractionextracted with ethyl acetate (2×20 ml)
  4. additionCombined organic extracts were treated with pyrrolidine (0.1 ml) and after 1 hour
  5. dry with materialwere dried over anhydrous magnesium sulphate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe residue was purified by reverse-phase HPLC with gradient 0.1% aqueous ammonium acetate/acetonitrile elution

Sources & evidence

ORD record
ord-591e1c05c13a4552bee8983aefcbe9b0
Source dataset
uspto-grants-2008_06
Patent number
US07384950B2

Reaction notes

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