Sodium Carbonate → (3aS,8aR)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one

HRID 539120Notes

Reaction equation

HRID 539120 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[C@H:15]4[C:16]5[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=5[CH2:22][C@H:14]4[O:13][C:12]3=[O:23])=[N:7][C:6]=12.[F:24][C:25]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[CH:27][C:26]=1[C:40]1[N:44]=[CH:43][N:42]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[N:41]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.CCOC(C)=O.O1CCOCC1>[F:24][C:25]1[CH:30]=[C:29]([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[CH:9][C:8]([N:11]4[C@H:15]5[C:16]6[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=6[CH2:22][C@H:14]5[O:13][C:12]4=[O:23])=[N:7][C:6]=23)[CH:28]=[CH:27][C:26]=1[C:40]1[N:44]=[CH:43][N:42]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[N:41]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 67034012HCID 67034012, compoundHCID 67034386(3aS,8aR)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one

Product 1

HCID 67034771(3aS,8aR)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-oneYield 28.7%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To (3aS,8aR)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one (100 mg, 0.269 mmol) were added 3-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazole (147 mg, 0.350 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (15.6 mg, 0.0269 mmol), Pd2 dba3 (12.3 mg, 0.0135 mmol), dioxane (1.2 mL) and 2M Na2CO3 (0.2 mL). The reaction was stirred for 2 hours at 80° C. in a sealed tube. After cooling, EtOAc and water were added. The organic phase was washed with brine and dried over MgSO4. The residue was purified by reverse phase chromatography (SP4, 12M, water/CH3CN 90:10 to 0:100, 20 column volumes) to yield (3aS,8aR)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one (45 mg, 28.6% yield) as a pale yellow solid.

Workup

  1. temperatureAfter cooling
  2. washThe organic phase was washed with brine
  3. dry with materialdried over MgSO4
  4. customThe residue was purified by reverse phase chromatography (SP4, 12M, water/CH3CN 90:10 to 0:100, 20 column volumes)

Sources & evidence

ORD record
ord-06eeb33fc1c04beeaaec7fcabb20044f
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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