Hydrazine → 6-[(3,5-Dimethyl-1H-pyrazol-4-yl)methyl]-1-isobutyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxylic acid

HRID 131564Notes

Reaction equation

HRID 131564 reaction equation
[C:1](=[O:4])([O-])[O-:2].[K+].[K+].ClC1N=C(C)N([CH2:14][C:15]2[S:30][C:18]3[N:19]([CH2:26][CH:27]([CH3:29])[CH3:28])[C:20](=[O:25])[N:21]([CH3:24])[C:22](=[O:23])[C:17]=3[C:16]=2C(N2C[C@H](O)CO2)=O)C=1Cl.[CH3:40][C:41](=O)[CH2:42][C:43](=O)[CH3:44].[NH2:47][NH2:48]>ClCCl.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Co]Cl>[CH3:40][C:41]1[C:42]([CH2:14][C:15]2[S:30][C:18]3[N:19]([CH2:26][CH:27]([CH3:28])[CH3:29])[C:20](=[O:25])[N:21]([CH3:24])[C:22](=[O:23])[C:17]=3[C:16]=2[C:1]([OH:2])=[O:4])=[C:43]([CH3:44])[NH:48][N:47]=1

Participants

8

Reactant 4

HCID 9321HydrazineHCID 11430Potassium CarbonateHCID 31261AcetylacetoneHCID 101425596-[(4,5-Dichloro-2-methyl-1H-imidazol-1-yl)methyl]-5-[4-(S)-hydroxy-2-isoxazolidinylcarbonyl]-3-methyl-1-(isobutyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 161028626-[(3,5-Dimethyl-1H-pyrazol-4-yl)methyl]-1-isobutyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxylic acid

Reagents, catalysts & solvents 3

HCID 432080Dichlorocobalt;triphenylphosphaneCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Potassium carbonate (3.55 g) and dichlorobis(triphenylphosphine)cobalt(II) (0.1 g) were added to a stirred solution of the product of example 3, part a) (1 g) and 2,4-pentanedione (2.64 ml) in dichloromethane (30 ml) under nitrogen. After 48 h, aqueous hydrazine (35%, 2.33 ml) was added and the mixture stirred vigorously for 1 h, diluted with water (30 ml) and extracted with ethyl acetate (2×60 ml). Organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography over silica, eluting with ethyl acetate. The product was dissolved in tetrahydrofuran (20 ml) and methanol (3 ml) then treated with sodium hydroxide solution (1M, 2.57 ml). After 3 days, the mixture was evaporated under reduced pressure to ca. 5 ml, diluted with water (25 ml) and extracted with ethyl acetate (25 ml). The aqueous phase was acidified with hydrochloric acid and extracted with ethyl acetate (3×25 ml). Organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure to give the sub-title compound as a solid (0.23 g). MS(ESI) 391 [M+H]+. δ 1HDMSO 0.85 (6H, d), 2.05-2.18 (1H, m), 2.08 (6H, s), 3.17 (3H, s), 3.62 (2H, d), 3.71 (2H, s).

Workup

  1. extractionextracted with ethyl acetate (2×60 ml)
  2. dry with materialOrganic extracts were dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. customevaporated under reduced pressure
  5. customThe residue was purified by column chromatography over silica
  6. washeluting with ethyl acetate
  7. dissolutionThe product was dissolved in tetrahydrofuran (20 ml)
  8. additionmethanol (3 ml) then treated with sodium hydroxide solution (1M, 2.57 ml)
  9. waitAfter 3 days
  10. customthe mixture was evaporated under reduced pressure to ca. 5 ml
  11. additiondiluted with water (25 ml)
  12. extractionextracted with ethyl acetate (25 ml)
  13. extractionextracted with ethyl acetate (3×25 ml)
  14. dry with materialOrganic extracts were dried over anhydrous magnesium sulfate
  15. filtrationfiltered
  16. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-9c8fb6b28cef4f168075a6b66820ef60
Source dataset
uspto-grants-2008_06
Patent number
US07384950B2

Reaction notes

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