Cesium carbonate → HCID 67430540, compound

HRID 1040141Notes

Reaction equation

HRID 1040141 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[CH:5]=[CH:4][N:3]=1.[NH2:22][C:23]1[CH:24]=[C:25]([C:32]2[S:36][C:35]([C:37]3([OH:41])[CH2:40][CH2:39][CH2:38]3)=[N:34][CH:33]=2)[CH:26]=[C:27]([N+:29]([O-:31])=[O:30])[CH:28]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[OH:41][C:37]1([C:35]2[S:36][C:32]([C:25]3[CH:24]=[C:23]([NH:22][C:2]4[N:7]=[C:6]([O:8][CH:9]5[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]5)[CH:5]=[CH:4][N:3]=4)[CH:28]=[C:27]([N+:29]([O-:31])=[O:30])[CH:26]=3)=[CH:33][N:34]=2)[CH2:40][CH2:39][CH2:38]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 584562421-[5-(3-Amino-5-nitrophenyl)-1,3-thiazol-2-yl]cyclobutanolHCID 71629906tert-Butyl 4-((2-chloropyrimidin-4-yl)oxy)piperidine-1-carboxylate

Product 1

HCID 67430540HCID 67430540, compoundYield 70.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To the product from Step 1 (900 mg, 2.87 mmol) and Intermediate 22 (836 mg, 2.87 mmol) in dioxane (28 mL) was added palladium acetate (129 mg, 0.574 mmol), XantPhos (498 mg, 0.860 mmol) and cesium carbonate (1.87 g, 5.74 mmol). The mixture was degassed with Ar for 10 min and then heated at 100° C. for 20 h. After cooling to ambient temperature, the reaction mixture was filtered through celite and washed with ethyl acetate and methanol. After solvent removal, the residue was purified by column chromatography on silica gel (0-90%, ethyl acetate: 10:1 methanol in hexanes) to afford tert-butyl 4-{[2-({3-[2-(1-hydroxycyclobutyl)-1,3-thiazol-5-yl]-5-nitrophenyl}amino)pyrimidin-4-yl]oxy}piperidine-1-carboxylate (1.15 g, 2.02 mmol, 70%). MS ESI: [M+H]+ m/z 569.2.

Workup

  1. customThe mixture was degassed with Ar for 10 min
  2. temperatureAfter cooling to ambient temperature
  3. filtrationthe reaction mixture was filtered through celite
  4. washwashed with ethyl acetate and methanol
  5. customAfter solvent removal
  6. customthe residue was purified by column chromatography on silica gel (0-90%, ethyl acetate: 10:1 methanol in hexanes)

Sources & evidence

ORD record
ord-02cb1acb94384bebb506a8830a56d2d7
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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