Cesium carbonate → Tert-butyl 1-(7-(5,6-dimethoxypyridin-2-ylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamate

HRID 1410099Notes

Reaction equation

HRID 1410099 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])[N:13]=2)[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1.[NH:22]1[CH2:26][CH2:25][CH:24]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:23]1.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]>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][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[CH2:26][CH2:25][CH:24]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33])[CH2:23]3)[N:3]=2)=[N:13][C:14]=1[O:20][CH3:21]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866717895-chloro-N-(5,6-dimethoxypyridin-2-yl)thiazolo[5,4-d]pyrimidin-7-amine

Product 1

HCID 68379621Tert-butyl 1-(7-(5,6-dimethoxypyridin-2-ylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamateYield 51.8%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
95 °C

Procedure

To a stirred solution of 5-chloro-N-(5,6-dimethoxypyridin-2-yl)thiazolo[5,4-d]pyrimidin-7-amine (344 mg, 1.06 mmol), tert-butyl pyrrolidin-3-ylcarbamate (289 mg, 1.55 mmol), X-Phos (256 mg, 0.53 mmol) and Cs2CO3 (1.3 g, 3.9 mmol) in 120 mL of dioxane at room temperature under nitrogen was added Pd2(dba)3 (138 mg, 0.24 mmol) in one portion. Then the reaction was stirred at 95° C. under nitrogen for 24 hours. The solvent was evaporated and the residue was purified by silica gel chromatography (silica gel 200-300 mesh, eluting with a mixture of ethyl acetate and petroleum ether (2:1)) to give tert-butyl 1-(7-(5,6-dimethoxypyridin-2-ylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamate (260 mg, 51.7%) as an oil. LC-MS: 474.2 [M+H]+, tR=1.67 min.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by silica gel chromatography (silica gel 200-300 mesh
  3. washeluting with a mixture of ethyl acetate and petroleum ether (2:1))

Sources & evidence

ORD record
ord-c1e4efa11d6e4875b31bf370fe7a0517
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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