Cesium carbonate → (R)-tert-butyl 3-(3-(3-(pyridin-4-yl)-1-trityl-1H-indazol-5-yl)-1H-1,2,4-triazol-5-yl)piperidine-1-carboxylate

HRID 1465700Notes

Reaction equation

HRID 1465700 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[N:15]=[C:14]([C@@H:16]4[CH2:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]4)[NH:13][N:12]=3)[CH:9]=2)[N:4]([C:29]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:3]=1.[N:48]1[CH:53]=[CH:52][C:51](B(O)O)=[CH:50][CH:49]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[N:48]1[CH:53]=[CH:52][C:51]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]4[N:15]=[C:14]([C@@H:16]5[CH2:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]5)[NH:13][N:12]=4)[CH:9]=3)[N:4]([C:29]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[N:3]=2)=[CH:50][CH:49]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 86695578(R)-tert-butyl 3-(3-(3-bromo-1-trityl-1H-indazol-5-yl)-1H-1,2,4-triazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 86695579(R)-tert-butyl 3-(3-(3-(pyridin-4-yl)-1-trityl-1H-indazol-5-yl)-1H-1,2,4-triazol-5-yl)piperidine-1-carboxylateYield 86.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

Stirred a mixture of (R)-tert-butyl 3-(3-(3-bromo-1-trityl-1H-indazol-5-yl)-1H-1,2,4-triazol-5-yl)piperidine-1-carboxylate (500 mg, 0.72 mmol), pyridine 4-boronic acid (150 mg, 1.22 mmol), PdCl2dppf (30 mg, 0.036 mmol) and Cesium carbonate (400 mg, 1.23 mmol) in dioxane (9 mL) and water (1 mL) at 100° C. in a microwave oven for 2 hours. After cooling, diluted with water (50 ml), then extracted with DCM (100 ml). The combined organic layer was dried (Na2SO4), filtered and evaporated to yield crude product, which chromatographed on silica gel eluting with 30% v/v EtOAc/Hexanes to yield (R)-tert-butyl 3-(3-(3-(pyridin-4-yl)-1-trityl-1H-indazol-5-yl)-1H-1,2,4-triazol-5-yl)piperidine-1-carboxylate as a white solid (430 mg).

Workup

  1. temperatureAfter cooling
  2. extractionextracted with DCM (100 ml)
  3. dry with materialThe combined organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto yield crude product, which
  7. customchromatographed on silica gel eluting with 30% v/v EtOAc/Hexanes

Sources & evidence

ORD record
ord-a2e8f0aa64ff49c7a19b87fa5a3b1238
Source dataset
uspto-grants-2015_04
Patent number
US08999966B2

Reaction notes

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