Sodium hydride → 5-(4-(((4-methoxybenzyl)oxy)methyl)thiazol-2-yl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

HRID 2201319Notes

Reaction equation

HRID 2201319 reaction equation
[H-].[Na+].[OH:3][CH2:4][C:5]1[N:6]=[C:7]([C:10]2[N:11](COCC[Si](C)(C)C)[CH:12]=[C:13]3[C:18]=2[C:17](=[O:19])[N:16]([CH3:20])[C:15](=[O:21])[N:14]3[CH3:22])[S:8][CH:9]=1.[CH3:31][O:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37]Cl)=[CH:35][CH:34]=1>CN1C(=O)CCC1>[CH3:31][O:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][O:3][CH2:4][C:5]2[N:6]=[C:7]([C:10]3[NH:11][CH:12]=[C:13]4[C:18]=3[C:17](=[O:19])[N:16]([CH3:20])[C:15](=[O:21])[N:14]4[CH3:22])[S:8][CH:9]=2)=[CH:35][CH:34]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 699934-Methyloxybenzyl chloride2×HCID 867229335-(4-(Hydroxymethyl)thiazol-2-yl)-1,3-dimethyl-6-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

Product 1

HCID 1363484085-(4-(((4-methoxybenzyl)oxy)methyl)thiazol-2-yl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Sodium hydride (60% wt, 0.637 g, 15.93 mmol) was added portionwise to a solution of 5-(4-(hydroxymethyl)thiazol-2-yl)-1,3-dimethyl-6-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (step 2) (4.43 g, 7.97 mmol) NMP (Volume: 44 ml) at 0° C. and stirred for 1 hour. para-Methoxybenzyl chloride (1.404 ml, 10.36 mmol) was added and the mixture stirred at room temperature for 5 hours. Further portions of para-methoxybenzyl chloride (220 μl) and sodium hydride (60% wt, 64 mg) were added and the mixture stirred for a further 16 hours. The reaction was quenched at 0° C. with saturated NaHCO3(aq) (50 ml), diluted with water (200 ml) and EtOAc (100 ml) and the phases separated. The aqueous phase was extracted with EtOAc (3×100 ml). The combined organic extracts were washed with water (2×100 ml) and brine (100 ml), dried over sodium sulfate and evaporated under vacuum. Purification by chromatography on silica, eluting with 40-60% EtOAc/hexane afforded the title compound and 5-(4-(((4-methoxybenzyl)oxy)methyl)thiazol-2-yl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione as a mixture which was used without further purification.

Workup

  1. stirringthe mixture stirred at room temperature for 5 hours
  2. stirringthe mixture stirred for a further 16 hours
  3. customThe reaction was quenched at 0° C. with saturated NaHCO3(aq) (50 ml)
  4. additiondiluted with water (200 ml) and EtOAc (100 ml)
  5. customthe phases separated
  6. extractionThe aqueous phase was extracted with EtOAc (3×100 ml)
  7. washThe combined organic extracts were washed with water (2×100 ml) and brine (100 ml)
  8. dry with materialdried over sodium sulfate
  9. customevaporated under vacuum
  10. customPurification by chromatography on silica
  11. washeluting with 40-60% EtOAc/hexane

Sources & evidence

ORD record
ord-832cb0341d7e41dc9f7fdf62c4baafef
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

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