Cesium carbonate → Methyl 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-4-carboxylate

HRID 1410030Notes

Reaction equation

HRID 1410030 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.[NH:22]1[CH2:27][CH2:26][CH:25]([C:28]([O:30][CH3:31])=[O:29])[CH2:24][CH2:23]1.C([O-])([O-])=O.[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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.[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:22]3[CH2:27][CH2:26][CH:25]([C:28]([O:30][CH3:31])=[O:29])[CH2:24][CH2:23]3)[N:3]=2)[CH:17]=[CH:16][C:15]=1[O:18][CH3:19]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 424914Methyl isonipecotateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 715341855-chloro-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine

Product 1

HCID 68379345Methyl 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-4-carboxylateYield 56.3%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 5-chloro-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine (200 mg, 0.62 mmol), methyl piperidine-4-carboxylate (177 mg, 1.24 mmol), Cs2CO3 (404 mg, 1.24 mmol), X-Phos (20 mg, 0.042 mmol), Pd(dba)2 (20 mg, 0.035 mmol) in 30 mL of dioxane were stirred at 100° for 18 hours under N2 atmosphere. The excess of dioxane was removed under reduced pressure and the residue was purified by silica gel chromatography (eluting with a mixture of petroleum ether and ethyl acetate=3:1) to give methyl 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-4-carboxylate (150 mg, 56%) as a yellow solid. LC-MS: 430 [M+H]+, tR=1.63 min

Workup

  1. customThe excess of dioxane was removed under reduced pressure
  2. customthe residue was purified by silica gel chromatography (
  3. washeluting with a mixture of petroleum ether and ethyl acetate=3:1)

Sources & evidence

ORD record
ord-416366d7038f4d3aaa93eb19d5453b36
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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