Cesium carbonate → HCID 67430661, compound

HRID 1040139Notes

Reaction equation

HRID 1040139 reaction equation
Cl[C:2]1[N:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][N:3]=1.[NH2:10][C:11]1[CH:12]=[C:13]([C:18]2[S:22][C:21]([C:23]3([OH:27])[CH2:26][CH2:25][CH2:24]3)=[N:20][CH:19]=2)[CH:14]=[C:15]([CH3:17])[CH:16]=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>[CH3:17][C:15]1[CH:14]=[C:13]([C:18]2[S:22][C:21]([C:23]3([OH:27])[CH2:26][CH2:25][CH2:24]3)=[N:20][CH:19]=2)[CH:12]=[C:11]([NH:10][C:2]2[N:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][N:3]=2)[CH:16]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 164271482-Chloro-4-(methylthio)pyrimidine2×HCID 584563951-[5-(3-Amino-5-methylphenyl)-2-thiazolyl]cyclobutanol

Product 1

HCID 67430661HCID 67430661, compoundYield 92%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
85 °C

Procedure

To a mixture of 2-chloro-4-(methylsulfanyl)pyrimidine (Intermediate 28, 500 mg, 3.11 mmol) and Intermediate 15 (810 mg, 3.11 mmol) in dioxane (15 mL) was added palladium(II) acetate (70 mg, 0.311 mmol), XantPhos (270 mg, 0.467 mmol) and cesium carbonate (2 g, 6.23 mmol). The mixture was degassed for 10 min and then heated at 85° C. for 16 h. After cooling to ambient temperature, the reaction mixture was filtered over celite and was washed with DCM/MeOH. After solvent removal, the residue was purified by column chromatography on silica gel (10 to 100% 10:1 ethyl acetate: methanol in hexanes) to afford 1-[5-(3-methyl-5-{[4-(methylsulfanyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol (1.1 g, 2.86 mmol, 92%). MS ESI: [M+H]+ m/z 385.1.

Workup

  1. customThe mixture was degassed for 10 min
  2. temperatureAfter cooling to ambient temperature
  3. filtrationthe reaction mixture was filtered over celite
  4. washwas washed with DCM/MeOH
  5. customAfter solvent removal
  6. customthe residue was purified by column chromatography on silica gel (10 to 100% 10:1 ethyl acetate: methanol in hexanes)

Sources & evidence

ORD record
ord-513877586961448cba28c84a49405bec
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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