Cesium carbonate → HCID 178472377, compound

HRID 928146Notes

Reaction equation

HRID 928146 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([C@H:11]2[CH2:16][CH2:15][C@H:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:13][CH2:12]2)([OH:10])[CH2:8][F:9])=[N:4][CH:3]=1.[CH3:22][C:23]1[CH:24]=[C:25]([NH:38][C:39]2[N:44]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:42]=[CH:41][N:40]=2)[CH:26]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:28]=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+]>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].O.O1CCOCC1>[F:9][CH2:8][C:7]([C@H:11]1[CH2:16][CH2:15][C@H:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:13][CH2:12]1)([OH:10])[C:5]1[S:6][C:2]([C:27]2[CH:26]=[C:25]([NH:38][C:39]3[N:44]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:42]=[CH:41][N:40]=3)[CH:24]=[C:23]([CH3:22])[CH:28]=2)=[CH:3][N:4]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 58456089N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amineHCID 178472376HCID 178472376, compound

Product 1

HCID 178472377HCID 178472377, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Racemic ethyl trans-4-[1-(5-bromo-1,3-thiazol-2-yl)-2-fluoro-1-hydroxyethyl]cyclohexane-carboxylate (107 mg, 0.281 mmol), N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (231 mg, 0.610 mmol), X-Phos (56 mg, 0.120 mmol), Pd2(dba)3 (52 mg, 0.056 mmol), cesium carbonate (429 mg, 1.32 mmol), 1,4-dioxane (3.0 ml) and water (0.3 ml) were combined and the vial was evacuated and purged with nitrogen 3 times then heated to 100° C. for 2 h. The mixture was then filtered and diluted with EtOAc. The organic phase was washed with water, brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified on silica gel (0-10% MeOH in DCM) to afford racemic ethyl trans-4-{2-fluoro-1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}cyclohexanecarboxylate which was used without further purification. MS ESI calc'd. for C26H28F4N4O3S [M+H]+ 553. found 553.

Workup

  1. customthe vial was evacuated
  2. custompurged with nitrogen 3 times
  3. filtrationThe mixture was then filtered
  4. additiondiluted with EtOAc
  5. washThe organic phase was washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified on silica gel (0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-da5e36387072404d93045ba7d22b9ca0
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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