Dimethyl Sulfoxide → HCID 22257971, compound

HRID 1611042Notes

Reaction equation

HRID 1611042 reaction equation
CS(C)=O.[C:5](Cl)(=[O:9])[C:6](Cl)=O.OC[CH2:13][CH2:14][S:15][C:16]1[C:24]2[C:23](=[O:25])[N:22]([CH3:26])[C:21](=[O:27])[N:20]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:19]=2[S:18][C:17]=1[CH2:32][C:33]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:36]=[CH:35][CH:34]=1.C(N(CC)CC)C>ClCCl.CCOCC>[OH:9][CH:5]([CH3:6])[CH2:13][CH2:14][S:15][C:16]1[C:24]2[C:23](=[O:25])[N:22]([CH3:26])[C:21](=[O:27])[N:20]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:19]=2[S:18][C:17]=1[CH2:32][C:33]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:36]=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 52825395-[(3-Hydroxypropyl)sulfanyl]-1-isobutyl-3-methyl-6-(1-naphthylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 22257971HCID 22257971, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent3×

Procedure

A solution of dimethylsulfoxide (0.113 ml) in anhydrous dichloromethane (1 ml) was added to a solution of oxalyl chloride (0.093 ml) in anhydrous dichloromethane (5 ml) at −78° C. under nitrogen. After 5 minutes, a solution of 5-[(3-hydroxypropyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (0.25 g) in anhydrous dichloromethane (4 ml) was added dropwise. After 10 minutes, triethylamine (0.372 ml) was added and the mixture was warmed to room temperature. Ether (30 ml) was added and the mixture was washed with 2M hydrochloric acid (10 ml) then with saturated sodium hydrogen carbonate solution (10 ml), then dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was dissolved in anhydrous tetrahydrofuran (10 ml), cooled to −78° C. under nitrogen and treated with methyl magnesium chloride (3.0M is solution in tetrahydrofuran, 0.265 ml). The mixture was warmed to room temperature, then added to saturated sodium hydrogen carbonate solution (30 ml) and then extracted with ethyl acetate (2×30 ml). The organic extracts were dried over anhydrous magnesium sulfate, filtered through a small silica pad and evaporated. The residue was purified by preparative normal-phase HPLC with ethyl acetate/isohexane gradient elution followed by recrystallisation from ethyl acetate/isohexane to give the title compound (58 mg).

Workup

  1. waitAfter 10 minutes
  2. washthe mixture was washed with 2M hydrochloric acid (10 ml)
  3. dry with materialwith saturated sodium hydrogen carbonate solution (10 ml), then dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe residue was dissolved in anhydrous tetrahydrofuran (10 ml)
  7. temperaturecooled to −78° C. under nitrogen
  8. additiontreated with methyl magnesium chloride (3.0M is solution in tetrahydrofuran, 0.265 ml)
  9. temperatureThe mixture was warmed to room temperature
  10. additionadded to saturated sodium hydrogen carbonate solution (30 ml)
  11. extractionextracted with ethyl acetate (2×30 ml)
  12. dry with materialThe organic extracts were dried over anhydrous magnesium sulfate
  13. filtrationfiltered through a small silica pad
  14. customevaporated
  15. customThe residue was purified by preparative normal-phase HPLC with ethyl acetate/isohexane gradient elution
  16. customfollowed by recrystallisation from ethyl acetate/isohexane

Sources & evidence

ORD record
ord-3f968437ed5946ccad79e14aad9cf183
Source dataset
uspto-grants-2006_01
Patent number
US06984644B2

Reaction notes

Loading…