Sodium Carbonate → Methyl 3-(7-(3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate

HRID 1410091Notes

Reaction equation

HRID 1410091 reaction equation
[CH2:1]1[C:4]2([CH2:7][N:6]([C:8]3[CH:9]=[C:10]([NH:14][C:15]4[C:16]5[N:24]=[CH:23][S:22][C:17]=5[N:18]=[C:19](Cl)[N:20]=4)[CH:11]=[CH:12][CH:13]=3)[CH2:5]2)[CH2:3][O:2]1.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[C:35]([CH:40]=[CH:41][CH:42]=2)[C:36]([O:38][CH3:39])=[O:37])O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]1[C:4]2([CH2:7][N:6]([C:8]3[CH:9]=[C:10]([NH:14][C:15]4[C:16]5[N:24]=[CH:23][S:22][C:17]=5[N:18]=[C:19]([C:33]5[CH:34]=[C:35]([CH:40]=[CH:41][CH:42]=5)[C:36]([O:38][CH3:39])=[O:37])[N:20]=4)[CH:11]=[CH:12][CH:13]=3)[CH2:5]2)[CH2:3][O:2]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27346513-Methoxycarbonylphenylboronic acid pinacol esterHCID 86671788N-(3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenyl)-5-chlorothiazolo[5,4-d]pyrimidin-7-amine

Product 1

HCID 68379407Methyl 3-(7-(3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoateYield 30.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of N-(3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenyl)-5-chlorothiazolo[5,4-d]pyrimidin-7-amine (160 mg, 0.5 mmol) and methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (145 mg, 0.55 mmol) in 9 mL of 1,4-dioxane and 1 mL of water was added Na2CO3 (159 mg, 1.5 mmol) followed by Pd(PPh3)4 (58 mg) under nitrogen with stirring. The mixture was refluxed for 15 hours under nitrogen. After cooled, the solvent was evaporated by rotary evaporation. The residue was poured into water and extracted with EtOAc (3×10 mL). The organic layer was washed with brine and dried over Na2SO4. After filtration and concentration, the residue was purified by column chromatography on silica gel eluting with (petroleum ether EtOAc=1:1) to give methyl 3-(7-(3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate (70 mg, 30%). LC-MS: 460 [M+H]+, tR=1.74 min.

Workup

  1. temperatureThe mixture was refluxed for 15 hours under nitrogen
  2. temperatureAfter cooled
  3. customthe solvent was evaporated by rotary evaporation
  4. additionThe residue was poured into water
  5. extractionextracted with EtOAc (3×10 mL)
  6. washThe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationAfter filtration and concentration
  9. customthe residue was purified by column chromatography on silica gel eluting with (petroleum ether EtOAc=1:1)

Sources & evidence

ORD record
ord-29b4106f3e514613b5f4d3fdd3390135
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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