2-Bromo-4-chloro-1,3-thiazole → 6-(3-(4-Chlorothiazol-2-yl)-3-oxopropyl)-1,3-dimethyl-5-phenyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

HRID 2201219Notes

Reaction equation

HRID 2201219 reaction equation
[CH3:1][N:2]1[C:7]2=[CH:8][N:9]([CH2:17][CH2:18][C:19](N(OC)C)=[O:20])[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[C:6]2[C:5](=[O:25])[N:4]([CH3:26])[C:3]1=[O:27].Br[C:29]1[S:30][CH:31]=[C:32]([Cl:34])[N:33]=1>C1COCC1>[Cl:34][C:32]1[N:33]=[C:29]([C:19](=[O:20])[CH2:18][CH2:17][N:9]2[C:10]([C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=3)=[C:6]3[C:7]([N:2]([CH3:1])[C:3](=[O:27])[N:4]([CH3:26])[C:5]3=[O:25])=[CH:8]2)[S:30][CH:31]=1

Participants

4

Reactant 2

HCID 151419642-Bromo-4-chloro-1,3-thiazole2×HCID 867234563-(1,3-Dimethyl-2,4-dioxo-5-phenyl-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)-N-methoxy-N-methylpropanamide

Product 1

HCID 867234576-(3-(4-Chlorothiazol-2-yl)-3-oxopropyl)-1,3-dimethyl-5-phenyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Isopropylmagnesium chloride lithium chloride complex solution (1.3M, 2.93 mL, 3.81 mmol) was added dropwise to a solution of 3-(1,3-dimethyl-2,4-dioxo-5-phenyl-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)-N-methoxy-N-methylpropanamide (470 mg, 1.269 mmol) and 2-bromo-4-chlorothiazole (Intermediate Q) (252 mg, 1.269 mmol) in THF (20 mL). The mixture was stirred at room temperature for 45 mins. The reaction was quenched with saturated NH4Cl(aq) and extracted with EtOAc (2×). The combined organic extracts were washed with brine, dried over sodium sulfate and evaporated under vacuum. Purification by chromatography on silica, eluting with 20-70% EtOAc/hexane afforded the title compound.

Workup

  1. customThe reaction was quenched with saturated NH4Cl(aq)
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated under vacuum
  6. customPurification by chromatography on silica
  7. washeluting with 20-70% EtOAc/hexane

Sources & evidence

ORD record
ord-aa6c7e73973b4ffcb6ba19d966ea79bb
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

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