1,2-Dimethoxyethane → HCID 66743751, compound

HRID 2364041Notes

Reaction equation

HRID 2364041 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]3([CH2:15][CH2:14][CH2:13][CH2:12]3)[N:5]([CH2:16][CH3:17])[C:4]=2[CH:3]=1.[CH3:18][C:19]1[C:23](B2OC(C)(C)C(C)(C)O2)=[CH:22][N:21](C(OC(C)(C)C)=O)[N:20]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[CH2:16]([N:5]1[C:4]2[CH:3]=[C:2]([C:23]3[CH:22]=[N:21][NH:20][C:19]=3[CH3:18])[S:10][C:9]=2[C:8](=[O:11])[NH:7][C:6]21[CH2:15][CH2:14][CH2:13][CH2:12]2)[CH3:17]

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 53216815Tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-pyrazole-1-carboxylateHCID 66743184HCID 66743184, compound

Product 1

HCID 66743751HCID 66743751, compoundYield 54.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A flask was charged with 6′-bromo-1′-ethyl-1′H-spiro [cyclopentane-1,2′-thieno[3,2-d]pyrimidin]-4′(3′H)-one (158 mg, 0.50 mmol), tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (463 mg, 1.5 mmol), sodium carbonate (150 mg, 2.5 mmol), 1,2-dimethoxyethane (3.0 mL) and water (1.5 mL). The flask was purged with argon. Then, 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (41 mg, 0.050 mmol) was added to the mixture. The flask was purged with argon again. After stirring at 100° C. for 1 h, 8 M aqueous NaOH (0.5 mL) was added. After stirring at 100° C. for 1 h, organic materials were extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, 50:50 hexane/EtOAc to EtOAc), then crystallized from MeOH/EtOAc/hexane to give the title compound (86 mg, 54%) as a yellow solid:

Workup

  1. customThe flask was purged with argon
  2. customThe flask was purged with argon again
  3. addition8 M aqueous NaOH (0.5 mL) was added
  4. stirringAfter stirring at 100° C. for 1 h
  5. extractionorganic materials were extracted with EtOAc
  6. washThe combined extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customAfter removal of the solvent at reduced pressure
  10. customthe residue was purified by column chromatography (Purif, silica gel, 50:50 hexane/EtOAc to EtOAc)
  11. customcrystallized from MeOH/EtOAc/hexane

Sources & evidence

ORD record
ord-dc681f1631864a259a0cb89dcf02719e
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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