Potassium Carbonate → HCID 178461448, compound

HRID 1504351Notes

Reaction equation

HRID 1504351 reaction equation
[CH3:1][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]2[NH:15][CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22](B4OC(C)(C)C(C)(C)O4)=[CH:21][CH:20]=3)[N:18]=2)[CH2:3]1.Br[C:35]1[CH:62]=[CH:61][C:38]([C:39]([NH:41][C:42]2[CH:43]=[N:44][C:45]([N:48]3[CH2:53][CH2:52][N:51]([C:54](=[O:59])[C:55]([CH3:58])([CH3:57])[CH3:56])[CH2:50][C@H:49]3[CH3:60])=[CH:46][CH:47]=2)=[O:40])=[C:37]([F:63])[C:36]=1[O:64][C:65]([F:68])([F:67])[F:66].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]>[F:63][C:37]1[C:36]([O:64][C:65]([F:68])([F:67])[F:66])=[C:35]([C:22]2[CH:21]=[CH:20][C:19]([C:17]3[N:18]=[C:14]([C@@H:4]4[CH2:3][C@H:2]([CH3:1])[CH2:6][N:5]4[C:7]([O:9][C:10]([CH3:11])([CH3:13])[CH3:12])=[O:8])[NH:15][CH:16]=3)=[CH:24][CH:23]=2)[CH:62]=[CH:61][C:38]=1[C:39](=[O:40])[NH:41][C:42]1[CH:43]=[N:44][C:45]([N:48]2[CH2:53][CH2:52][N:51]([C:54](=[O:59])[C:55]([CH3:58])([CH3:57])[CH3:56])[CH2:50][C@H:49]2[CH3:60])=[CH:46][CH:47]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 86682819HCID 86682819, compoundHCID 178461443HCID 178461443, compound

Product 1

HCID 178461448HCID 178461448, compoundYield 71.7%

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 solution of (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 (68.6 mg, 0.15 mmol) and (R)-4-bromo-2-fluoro-N-(6-(2-methyl-4-pivaloylpiperazin-1-yl)pyridin-3-yl)-3-(trifluoromethoxy)benzamide (85 mg, 0.15 mmol, Preparation 52) and potassium carbonate (110 mg, 0.80 mmol) in a mixture of toluene (1.8 mL) and water (0.6 mL) was added PdCl2(dppf) (6.7 mg, 9.08 μmol). The mixture was sparged under nitrogen for 2 min and heated at 100° C. overnight and extracted with EtOAc and water. The organic layer was dried over sodium sulfate, filtered, concentrated, and purified by silica gel chromatography (12 g silica, 0-100% EtOAc:hexanes over 20 min), to provide the title intermediate (86.9 mg, 71% yield) as a yellow solid. (m/z): [M+H]+ calcd for C42H49F4N7O5 808.37. found 808.7.

Workup

  1. customThe mixture was sparged under nitrogen for 2 min
  2. extractionextracted with EtOAc and water
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography (12 g silica, 0-100% EtOAc:hexanes over 20 min)

Sources & evidence

ORD record
ord-b9051d62d61243e7ab0db193bdb76eec
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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