Potassium Carbonate → HCID 178461450, compound

HRID 1504350Notes

Reaction equation

HRID 1504350 reaction equation
Br[C:2]1[C:29]([O:30][C:31]([F:34])([F:33])[F:32])=[CH:28][C:5]([C:6]([NH:8][C:9]2[CH:10]=[N:11][C:12]([N:15]3[CH2:20][CH2:19][N:18]([C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:17][C@H:16]3[CH3:27])=[CH:13][CH:14]=2)=[O:7])=[CH:4][C:3]=1[Cl:35].[CH3:36][C@@H:37]1[CH2:41][N:40]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C@H:39]([C:49]2[NH:50][CH:51]=[C:52]([C:54]3[CH:59]=[CH:58][C:57](B4OC(C)(C)C(C)(C)O4)=[CH:56][CH:55]=3)[N:53]=2)[CH2:38]1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:35][C:3]1[CH:4]=[C:5]([C:6](=[O:7])[NH:8][C:9]2[CH:10]=[N:11][C:12]([N:15]3[CH2:20][CH2:19][N:18]([C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:17][C@H:16]3[CH3:27])=[CH:13][CH:14]=2)[CH:28]=[C:29]([O:30][C:31]([F:34])([F:33])[F:32])[C:2]=1[C:57]1[CH:56]=[CH:55][C:54]([C:52]2[N:53]=[C:49]([C@@H:39]3[CH2:38][C@H:37]([CH3:36])[CH2:41][N:40]3[C:42]([O:44][C:45]([CH3:46])([CH3:48])[CH3:47])=[O:43])[NH:50][CH:51]=2)=[CH:59][CH:58]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 89541304HCID 89541304, compoundHCID 178461443HCID 178461443, compound

Product 1

HCID 178461450HCID 178461450, compoundYield 51%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of (R)-4-bromo-3-chloro-N-(6-(2-methyl-4-pivaloylpiperazin-1-yl)pyridin-3-yl)-5-(trifluoromethoxy)benzamide (80.3 mg, 0.14 mmol; Preparation 51) and (2S,4S)-tert-butyl 4-methyl-2-(4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (63.0 mg, 0.14 mmol) in a mixture of toluene (0.9 mL) and water (0.3 mL) was added potassium carbonate (86 mg, 0.63 mmol). The reaction mixture was flushed with nitrogen, PdCl2(dppf) (6.1 mg, 8.34 μmol) was added. The reaction mixture was capped, heated at 100° C. overnight, cooled to RT and partitioned between EtOAc (5 mL) and water (2 mL). The organic layer was dried over sodium sulfate, filtered and concentrated to give a brown oil, which was purified by silica gel chromatography (12 g silica gel, 0-100% EtOAc/hexanes). Desired fractions were combined and concentrated to give the title intermediate (58.1 mg, 51% yield) as a yellowish oil. (m/z): [M+H]+ calcd for C42H49ClF3N2O5 824.34. found 824.

Workup

  1. additionwas added
  2. customThe reaction mixture was capped
  3. temperaturecooled to RT
  4. custompartitioned between EtOAc (5 mL) and water (2 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a brown oil, which
  9. customwas purified by silica gel chromatography (12 g silica gel, 0-100% EtOAc/hexanes)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-e5c950758c9647549c91b050d7da94c7
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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