Potassium Carbonate → HCID 66745204, compound

HRID 1959463Notes

Reaction equation

HRID 1959463 reaction equation
Br[C:2]1[N:3]=[C:4]([C:23]2[O:24][C:25]([C:28]3[CH:33]=[CH:32][C:31]([CH2:34][Br:35])=[CH:30][CH:29]=3)=[N:26][N:27]=2)[C:5]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:44]2[CH2:45][CH2:46][N:47]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:48][CH:49]=2)O1.C(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)(C)C.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.Cl[Pd]Cl.O>[C:11]([O:10][C:9]([N:8]([C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[C:5]1[N:6]=[CH:7][C:2]([C:44]2[CH2:49][CH2:48][N:47]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:46][CH:45]=2)=[N:3][C:4]=1[C:23]1[O:24][C:25]([C:28]2[CH:33]=[CH:32][C:31]([CH2:34][Br:35])=[CH:30][CH:29]=2)=[N:26][N:27]=1)=[O:15])([CH3:13])([CH3:14])[CH3:12]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 11714598(4-(N,N-Dimethylamino)phenyl)di-tert-butyl phosphineHCID 86662088HCID 86662088, compound

Product 1

HCID 66745204HCID 66745204, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of tert-butyl N-[5-bromo-3-[5-[4-(bromomethyl)phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N-tert-butoxycarbonyl-carbamate (500 mg, 0.82 mmol) in toluene (4.4 mL)/water (484 μL) was added tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (304 mg, 1.0 mmol) followed by the addition of 4-ditert-butylphosphanyl-N,N-dimethyl-aniline; dichloropalladium (58 mg, 0.082 mmol) and K2CO3 (226 mg, 1.6 mmol). The reaction mixture was heated at 60° C. for 3 h. The reaction mixture was partitioned between DCM and saturated aqueous NaHCO3, the layers were separated and the aqueous layer was extracted with DCM. The combined organics were dried over Na2SO4, filtered and concentrated to brown oil. The crude material was purified by silica gel column chromatography using 0-20% EtOAc in hexanes to yield tert-butyl 4-[5-[bis(tert-butoxycarbonyl)amino]-6-[5-[4-(bromomethyl)phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-3,6-dihydro-2H-pyridine-1-carboxylate (350 mg, 60%). 1HNMR (400 MHz, CDCl3) δ 8.74 (s, 1H), 8.22 (d, J=33.8 Hz, 2H), 7.59 (d, J=8.2 Hz, 2H), 6.92 (s, 1H), 4.54 (s, 2H), 4.24 (s, 2H), 3.73 (t, J=5.5 Hz, 2H), 2.79 (d, J=0.8 Hz, 2H), 1.37 (s, 18H), 1.24 (s, 9H).

Workup

  1. customThe reaction mixture was partitioned between DCM and saturated aqueous NaHCO3
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with DCM
  4. dry with materialThe combined organics were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to brown oil
  7. customThe crude material was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0c303543734e4a4c9d34a5ee4b41c7de
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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