Cesium carbonate → HCID 68379089, compound

HRID 1410094Notes

Reaction equation

HRID 1410094 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=2)[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1.Cl.[CH3:23][O:24][C:25]([CH:27]1[CH2:31][CH2:30][NH:29][CH2:28]1)=[O:26].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:21][O:20][C:14]1[CH:13]=[C:12]([NH:11][C:4]2[C:5]3[N:10]=[CH:9][S:8][C:6]=3[N:7]=[C:2]([N:29]3[CH2:30][CH2:31][CH:27]([C:25]([O:24][CH3:23])=[O:26])[CH2:28]3)[N:3]=2)[CH:17]=[CH:16][C:15]=1[O:18][CH3:19]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 19261352Methyl pyrrolidine-3-carboxylate hydrochlorideHCID 715341855-chloro-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine

Product 1

HCID 68379089HCID 68379089, compoundYield 88.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 5-chloro-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine (140 mg, 0.433 mmol), methylpyrrolidine-3-carboxylate hydrochloride (107.7 mg, 0.65 mmol), X-Phos (115 mg, 0.24 mmol) and Cs2CO3 (580 mg, 1.78 mmol) in 60 mL of dry dioxane was added Pd2(dba)3 (60 mg, 0.065 mmol) in one portion at room temperature under nitrogen. Then the reaction mixture was degassed by nitrogen for 15 minutes. The mixture was then stirred at 95° C. under nitrogen for 24 hours. The solvent was evaporated at 40° C. at reduced pressure and the residue was purified by silica gel chromatography (silica gel 200-300 mesh, eluting a mixture of ethyl acetate and petroleum ether (2:1)) to give methyl 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidine-3-carboxylate (160 mg, 88.7%) as a yellow solid. LC-MS: 416.1 [M+H]+, tR=1.60 min.

Workup

  1. customThen the reaction mixture was degassed by nitrogen for 15 minutes
  2. customThe solvent was evaporated at 40° C. at reduced pressure
  3. customthe residue was purified by silica gel chromatography (silica gel 200-300 mesh
  4. washeluting
  5. additiona mixture of ethyl acetate and petroleum ether (2:1))

Sources & evidence

ORD record
ord-b9b94044658c4ca6a11638c9ce923341
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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