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

HRID 1410008Notes

Reaction equation

HRID 1410008 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][CH2:25][CH:24]([C:28]([O:30][CH3:31])=[O:29])[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.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:22]3[CH2:27][CH2:26][CH2:25][CH:24]([C:28]([O:30][CH3:31])=[O:29])[CH2:23]3)[N:3]=2)[CH:17]=[CH:16][C:15]=1[O:18][CH3:19]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 351626Methyl piperidine-3-carboxylateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 715341855-chloro-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine

Product 1

HCID 68379218Methyl 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylateYield 56%

Reagents, catalysts & solvents 2

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

Procedure

To a solution of (5-chloro-thiazolo[5,4-d]pyrimidin-7-yl)-(3,4-dimethoxy-phenyl)-amine (80 mg, 0.25 mmol) in 10 mL of dioxane, methyl piperidine-3-carboxylate (107 mg, 0.75 mmol), Cs2CO3 (163 mg, 0.50 mmol), X-Phos (47.6 mg, 0.1 mmol) were added. After degassed three times under nitrogen, Pd2(dba)3 (28 mg, 0.05 mmol) was added. The resulting mixture was degassed one more time, and stirred at reflux overnight. The excess of dioxane was removed under reduced pressure and the residue was purified by silica gel chromatography (200-300 mesh, petroleum ether:ethyl acetate=1:1) to give methyl 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylate (60 mg, 56%) as an oil, which was solidified after standing overnight. 1H NMR (300 MHz, CDCl3): δ 8.41 (s, 1H), 7.77 (s, 1H), 7.64 (s, 1H), 7.08 (d, 1H, J=9.0 Hz), 6.88 (d, 1H, J=8.7 Hz), 4.92-4.87 (m, 1H), 4.68-4.64 (m, 1H), 3.93 (s, 3H), 3.91 (s, 3H), 3.71 (s, 3H), 3.30-3.22 (m, 1H), 3.10-3.09 (m, 1H), 2.60-2.59 (m, 1H), 2.11-2.06 (m, 1H), 1.85-1.60 (m, 3H). LC-MS: 430.1 [M+H]+, 452.1 [M+Na]+, tR=1.63 min.

Workup

  1. customAfter degassed three times under nitrogen
  2. customThe resulting mixture was degassed one more time
  3. temperatureat reflux overnight
  4. customThe excess of dioxane was removed under reduced pressure
  5. customthe residue was purified by silica gel chromatography (200-300 mesh, petroleum ether:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-442c1bcfb77640d7ab0f1e3611d7b952
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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