Ethyl 2-bromo-1,3-thiazole-4-carboxylate → Ethyl 2-(1,3-dimethyl-2,4-dioxo-6-(2-(tritylthio)ethyl)-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-5-yl)thiazole-4-carboxylate

HRID 2201291Notes

Reaction equation

HRID 2201291 reaction equation
[CH3:1][N:2]1[C:7]2=[CH:8][N:9]([CH2:14][CH2:15][S:16][C:17]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:10](B(O)O)=[C:6]2[C:5](=[O:36])[N:4]([CH3:37])[C:3]1=[O:38].Br[C:40]1[S:41][CH:42]=[C:43]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[N:44]=1.C(=O)([O-])O.[Na+]>C(OCCCC)(=O)C.O.C(Cl)Cl>[CH3:1][N:2]1[C:7]2=[CH:8][N:9]([CH2:14][CH2:15][S:16][C:17]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:10]([C:40]3[S:41][CH:42]=[C:43]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[N:44]=3)=[C:6]2[C:5](=[O:36])[N:4]([CH3:37])[C:3]1=[O:38]

Participants

7

Reactant 3

HCID 353965Ethyl 2-bromo-1,3-thiazole-4-carboxylateHCID 516892Sodium BicarbonateHCID 867235221,3-Dimethyl-2,4-dioxo-6-(2-(tritylthio)ethyl)-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-5-ylboronic acid2×

Product 1

HCID 86723525Ethyl 2-(1,3-dimethyl-2,4-dioxo-6-(2-(tritylthio)ethyl)-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-5-yl)thiazole-4-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 31272Butyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

(1,3-dimethyl-2,4-dioxo-6-(2-(tritylthio)ethyl)-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-5-yl)boronic acid (Intermediate F) (1001 mg, 1.906 mmol), ethyl 2-bromothiazole-4-carboxylate (409 mg, 1.732 mmol), sodium hydrogen carbonate (291 mg, 3.46 mmol) and Pd-118 (113 mg, 0.173 mmol) were suspended in n-butyl acetate (12.3 ml) and heated to 80° C. Water (3.08 ml) was then added and the mixture heated at 80° C. for 21 hours. The mixture was then cooled to room temperature and diluted with water (100 ml) and DCM (100 ml). The mixture was extracted with DCM (3×100 ml) and the combined organic extracts were washed with water (50 ml) and brine (50 ml). Silica-TMT (30 g) was added and the mixture stirred at room temperature for 5 mins, then filtered. The residue was rinsed with DCM (20 ml) and the filtrates evaporated under vacuum. The resultant residue was rinsed with diethyl ether and filtered to afford the title compound.

Workup

  1. temperaturethe mixture heated at 80° C. for 21 hours
  2. temperatureThe mixture was then cooled to room temperature
  3. extractionThe mixture was extracted with DCM (3×100 ml)
  4. washthe combined organic extracts were washed with water (50 ml) and brine (50 ml)
  5. additionSilica-TMT (30 g) was added
  6. filtrationfiltered
  7. washThe residue was rinsed with DCM (20 ml)
  8. customthe filtrates evaporated under vacuum
  9. washThe resultant residue was rinsed with diethyl ether
  10. filtrationfiltered

Sources & evidence

ORD record
ord-f2c35d63d18e41b990d39c47b4ca98f8
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

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