Cesium carbonate → Ibrexafungerp

HRID 1931551Notes

Reaction equation

HRID 1931551 reaction equation
[NH2:1][C@:2]([CH3:48])([C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:3][O:4][C@@H:5]1[C@@:12]2([CH3:37])[C@@H:13]3[CH2:14][CH2:15][C@H:16]4[C:25]([C@@:8]3([CH2:9][O:10][CH2:11]2)[CH2:7][C@H:6]1[N:38]1[C:42](Br)=[N:41][CH:40]=[N:39]1)=[CH:24][CH2:23][C@:22]1([CH3:26])[C@:17]4([CH3:36])[CH2:18][CH2:19][C@@:20]([C@H:31]([CH3:35])[CH:32]([CH3:34])[CH3:33])([CH3:30])[C@H:21]1[C:27]([OH:29])=[O:28].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:63]2[CH:68]=[CH:67][N:66]=[CH:65][CH:64]=2)O1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C@:2]([CH3:48])([C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:3][O:4][C@@H:5]1[C@@:12]2([CH3:37])[C@@H:13]3[CH2:14][CH2:15][C@H:16]4[C:25]([C@@:8]3([CH2:9][O:10][CH2:11]2)[CH2:7][C@H:6]1[N:38]1[C:42]([C:63]2[CH:68]=[CH:67][N:66]=[CH:65][CH:64]=2)=[N:41][CH:40]=[N:39]1)=[CH:24][CH2:23][C@:22]1([CH3:26])[C@:17]4([CH3:36])[CH2:18][CH2:19][C@@:20]([C@H:31]([CH3:35])[CH:32]([CH3:34])[CH3:33])([CH3:30])[C@H:21]1[C:27]([OH:29])=[O:28]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 27346484-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59312614HCID 59312614, compound

Product 1

HCID 46871657IbrexafungerpYield 18.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

A suspension of (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[(2R)-2-amino-2,3,3-trimethylbutyl]oxy]-14-(5-bromo-1H-1,2,4-triazol-1-yl)-8-[(1R)-1,2-dimethylpropyl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid (Example 11, 37.2 mg, 0.044 mmol), cesium carbonate (255 mg, 0.78 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (129 mg, 0.63 mmol), palladium (II) acetate (14.4 mg, 0.06 mmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (24 mg, 0.05 mmol) in dioxane (1.2 mL) was blanketed with nitrogen and heated in a microwave at 150° C. for 45 minutes. The mixture was cooled to room temperature, filtered and purified by reverse phase HPLC using a 19×150 mm Sunfire Preparative C18 OBD column eluting with acetonitrile/water+0.1% TFA. Product fractions were evaporated and freeze-dried from a mixture of ethanol and benzene to give the title compound (5.9 mg) as a white solid (trifluoroacetic acid salt).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationfiltered
  3. custompurified by reverse phase HPLC
  4. washeluting with acetonitrile/water+0.1% TFA
  5. customProduct fractions were evaporated
  6. dry with materialfreeze-dried from a mixture of ethanol and benzene

Sources & evidence

ORD record
ord-f22afc023875498c94652dc1215f8a12
Source dataset
uspto-grants-2012_05
Patent number
US08188085B2

Reaction notes

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