Cesium carbonate → HCID 117842857, compound

HRID 2209233Notes

Reaction equation

HRID 2209233 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([N:11]2[CH2:15][C@H:14]([C@H:16]([O:18][C:19]3[C:20]4[N:21]([N:34]=[CH:35][CH:36]=4)[CH:22]=[C:23](B4OC(C)(C)C(C)(C)O4)[CH:24]=3)[CH3:17])[CH2:13][C:12]2=[O:37])[CH3:10])=[CH:5][CH:4]=1.Br[C:39]1[N:44]=[CH:43][C:42]([N:45]2[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][CH2:46]2)=[CH:41][CH:40]=1.C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.O.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([N:11]2[C:12](=[O:37])[CH2:13][C@@H:14]([C@H:16]([O:18][C:19]3[C:20]4[N:21]([N:34]=[CH:35][CH:36]=4)[CH:22]=[C:23]([C:39]4[N:44]=[CH:43][C:42]([N:45]5[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][CH2:46]5)=[CH:41][CH:40]=4)[CH:24]=3)[CH3:17])[CH2:15]2)[CH3:10])=[CH:5][CH:4]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 11530243Tert-butyl 4-(6-bromopyridin-3-yl)piperazine-1-carboxylateHCID 123800714HCID 123800714, compound

Product 1

HCID 117842857HCID 117842857, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

(R)-1-((R)-1-(4-methoxyphenyl)ethyl)-4-((R)-1-((6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one 6.19 (55.0 mg, 0.109 mmol), tert-butyl 4-(6-bromopyridin-3-yl)piperazine-1-carboxylate 7.13 (65.2 mg, 0.190 mmol) and Cs2CO3 (106 mg, 0.326 mmol) were dissolved in 1,2-dimethoxyethane (3.0 mL) and water (1.5 mL). The mixture was degassed for 5 minutes. PEPPSI-IPr catalyst (7.42 mg, 0.0109 mmol) was added and the mixture was heated for 1 h at 90° C. The reaction was cooled and diluted with EtOAc and water. The layers were separated and the organic layer was dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (50 to 100% EtOAc in hexanes) to provide tert-butyl 4-(6-(4-((R)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyridin-6-yl)pyridin-3-yl)piperazine-1-carboxylate 6.20.

Workup

  1. customThe mixture was degassed for 5 minutes
  2. temperatureThe reaction was cooled
  3. customThe layers were separated
  4. dry with materialthe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography (50 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-61118a58998e4705832e6444015f1343
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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