1,2-Dimethoxyethane → HCID 66744046, compound

HRID 2364019Notes

Reaction equation

HRID 2364019 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([CH3:13])([CH3:12])[N:5]([CH2:14][C:15]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:16])[C:4]=2[CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].COCCOC.CC1(C)C(C)(C)OB([C:43]2[CH:44]=[N:45][N:46](C(OC(C)(C)C)=O)[CH:47]=2)O1>O>[CH3:12][C:6]1([CH3:13])[N:5]([CH2:14][C:15]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[O:16])[C:4]2[CH:3]=[C:2]([C:43]3[CH:44]=[N:45][NH:46][CH:47]=3)[S:10][C:9]=2[C:8](=[O:11])[NH:7]1

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 66743494HCID 66743494, compound

Product 1

HCID 66744046HCID 66744046, compoundYield 27.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A flask was charged with 6-bromo-2,2-dimethyl-1-(2-(morpholin-4-yl)-2-oxoethyl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (115 mg, 0.296 mmol), Na2CO3 (89 mg, 1.48 mmol), 1,2-dimethoxyethane (2 mL), water (1 mL) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (261 mg, 0.888 mmol). The flask was purged with argon. Then, 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (24 mg, 0.0296 mmol) was added to the mixture. The flask was purged with argon again. After stirring at 100° C. for 3 h, water and EtOAc were added to quench the reaction. The insoluble materials were filtered off, and NaCl was added to the filtrate. The organic materials were extracted with EtOAc/THF, and the extract was concentrated under reduced pressure. The residue was purified by column chromatography (Purif, silica gel, EtOAc to 80:20 EtOAc/MeOH), then crystallized from MeOH/EtOAc/hexane to give the title compound (31 mg, 27%) as a pale brown solid:

Workup

  1. customThe flask was purged with argon
  2. customThe flask was purged with argon again
  3. additionwater and EtOAc were added
  4. customto quench
  5. customthe reaction
  6. filtrationThe insoluble materials were filtered off
  7. additionNaCl was added to the filtrate
  8. extractionThe organic materials were extracted with EtOAc/THF
  9. concentrationthe extract was concentrated under reduced pressure
  10. customThe residue was purified by column chromatography (Purif, silica gel, EtOAc to 80:20 EtOAc/MeOH)
  11. customcrystallized from MeOH/EtOAc/hexane

Sources & evidence

ORD record
ord-9c76b7fbea6a4802ae6b97e67702f94e
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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