Potassium Carbonate → (S)-tert-Butyl 4-(1-amino-3-(4-(2-methyl-1-oxoisoindolin-5-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216977Notes

Reaction equation

HRID 216977 reaction equation
C(=O)([O-])[O-].[K+].[K+].[NH2:7][C:8](=[O:35])[C@@H:9]([NH:18][C:19]([C:21]1([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1)=[O:20])[CH2:10][C:11]1[CH:16]=[CH:15][C:14](I)=[CH:13][CH:12]=1.[CH3:36][N:37]1[CH2:45][C:44]2[C:39](=[CH:40][CH:41]=[C:42](B(O)O)[CH:43]=2)[C:38]1=[O:49]>O.C(#N)C>[NH2:7][C:8](=[O:35])[C@@H:9]([NH:18][C:19]([C:21]1([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1)=[O:20])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:42]2[CH:43]=[C:44]3[C:39](=[CH:40][CH:41]=2)[C:38](=[O:49])[N:37]([CH3:36])[CH2:45]3)=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 59568595(S)-tert-Butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateHCID 59568610(2-Methyl-1-oxoisoindolin-5-yl)boronic acid

Product 1

HCID 59568583(S)-tert-Butyl 4-(1-amino-3-(4-(2-methyl-1-oxoisoindolin-5-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateYield 87.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Potassium carbonate (276 mg) in water (2.0 mL) was added to (S)-tert-butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 1, step (iii), 517 mg), 2-methyl-1-oxoisoindolin-5-ylboronic acid (Example 31, step (iii), 191 mg) and 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (98 mg) in degassed acetonitrile (12 mL) at 20° C. under nitrogen. The resulting solution was stirred at 80° C. for 30 min. The reaction mixture was cooled, filtered and diluted with dichloromethane, and washed with water. The organic extract was dried over magnesium sulfate, filtered and evaporated to afford crude product. The crude product was purified by chromatography in silica eluting with methanol/ethyl acetate (5:95 to 15:85). Pure fractions were evaporated to dryness to afford the sub-titled compound (469 mg).

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered
  3. additiondiluted with dichloromethane
  4. washwashed with water
  5. extractionThe organic extract
  6. dry with materialwas dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customto afford crude product
  10. customThe crude product was purified by chromatography in silica eluting with methanol/ethyl acetate (5:95 to 15:85)
  11. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-5779731748a2488eb60f2027d732712c
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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