Dimethylformamide → HCID 18366607, compound

HRID 379582Notes

Reaction equation

HRID 379582 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH3:9][N:10]1[C:15](=[O:16])[C:14]2[C:17]([C:20]([N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)=[O:21])=[CH:18][S:19][C:13]=2[N:12]([CH2:27][CH:28]([CH3:30])[CH3:29])[C:11]1=[O:31].CN(C)[CH:34]=[O:35].C(=O)(O)[O-].[Na+]>O1CCCC1>[OH:35][CH2:34][C:18]1[S:19][C:13]2[N:12]([CH2:27][CH:28]([CH3:29])[CH3:30])[C:11](=[O:31])[N:10]([CH3:9])[C:15](=[O:16])[C:14]=2[C:17]=1[C:20]([N:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1)=[O:21]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 2724682Lithium diisopropylamideHCID 18366614HCID 18366614, compound

Product 1

HCID 18366607HCID 18366607, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of lithium diisopropylamide (2.50 mmol) in anhydrous tetrahydrofuran (5 ml) was added dropwise to a stirred solution of 1-{[1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]carbonyl}pyrrolidine (0.42 g) in anhydrous tetrahydrofuran (10 ml) at −78° C. under nitrogen. After 10 minutes, anhydrous dimethylformamide (0.29 ml) was added. After a further 2 hours at −78° C., saturated aqueous sodium bicarbonate solution was added and the mixture was warmed to room temperature and then extracted with ethyl acetate (3×20 ml). The organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was redissolved in methanol/acetic acid (10:1, 11 ml) and sodium borohydride (1 g) was added portionwise over 1 hour with stirring. After a further 1 hour, water (50 ml) was added, the. mixture was neutralised with sodium bicarbonate and extracted with ethyl acetate (4×25 ml). The combined organic extracts were dried over anhydrous magnesium sulfate and filtered through a silica pad which was washed with ethyl acetate/methanol (19:1). The filtrate was evaporated and the residue was purified by normal-phase preparative HPLC with gradient dichloromethane/ethanol elution to give the subtitle compound (0.22 g) as a solid.

Workup

  1. waitAfter a further 2 hours at −78° C.
  2. extractionextracted with ethyl acetate (3×20 ml)
  3. dry with materialThe organic extracts were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe residue was redissolved in methanol/acetic acid (10:1, 11 ml)
  7. additionsodium borohydride (1 g) was added portionwise over 1 hour
  8. waitAfter a further 1 hour
  9. additionwater (50 ml) was added
  10. extractionextracted with ethyl acetate (4×25 ml)
  11. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  12. filtrationfiltered through a silica pad which
  13. washwas washed with ethyl acetate/methanol (19:1)
  14. customThe filtrate was evaporated
  15. customthe residue was purified by normal-phase preparative HPLC with gradient dichloromethane/ethanol elution

Sources & evidence

ORD record
ord-c954fa9507d948ce85377edae8bd6c26
Source dataset
uspto-grants-2001_10
Patent number
US06300334B1

Reaction notes

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