Cesium carbonate → di-tert-butyl 1-{1-benzyl-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-1H-pyrrolo[3,2-b]pyridin-5-yl}hydrazine-1,2-dicarboxylate

HRID 628308Notes

Reaction equation

HRID 628308 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[N:12][C:13](Cl)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:18]1[CH:19]=[N:20][N:21]([CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[CH:22]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:29]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32].C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.NC1C=CC=CC=1C1C=CC=CC=1[Pd]Cl>[CH2:1]([N:8]1[C:16]2[C:11](=[N:12][C:13]([N:29]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[NH:30][C:31]([O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:32])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:18]1[CH:19]=[N:20][N:21]([CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[CH:22]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 85431Di-tert-butyl bicarbamateHCID 1181595721-benzyl-5-chloro-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-1H-pyrrolo[3,2-b]pyridine

Product 1

HCID 118159619di-tert-butyl 1-{1-benzyl-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-1H-pyrrolo[3,2-b]pyridin-5-yl}hydrazine-1,2-dicarboxylate

Reagents, catalysts & solvents 2

HCID 178439015HCID 178439015, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

1-Benzyl-5-chloro-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-1H-pyrrolo[3,2-b]pyridine (0.106 g, 0.270 mmol, from Step 1), di-tert-butyl hydrazine-1,2-dicarboxylate (0.069 g, 0.30 mmol) and Cs2CO3 (0.088 g, 0.27 mmol) were combined in toluene (2.4 mL) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (0.021 g, 0.027 mmol) was added. The mixture was degassed by a stream of nitrogen through the solution for 10 minutes. The reaction was heated to 110° C. for 1.5 hours, at which time additional reagents and catalyst were added (same of each as the initial quantities) and the mixture was degassed again and was heated in the microwave to 140° C. for 10 minutes. The reaction mixture was partitioned between EtOAc and water, extracted three times and the combined extracts were dried over sodium sulfate, filtered, and concentrated. The resulting product was purified via preparative HPLC-MS (C18 eluting with a gradient of MeCN and H2O containing 0.15% NH4OH). Yield (71 mg, 44%).

Workup

  1. customThe mixture was degassed by a stream of nitrogen through the solution for 10 minutes
  2. additionwere added (same of each as the initial quantities) and the mixture
  3. customwas degassed again
  4. temperaturewas heated in the microwave to 140° C. for 10 minutes
  5. customThe reaction mixture was partitioned between EtOAc and water
  6. extractionextracted three times
  7. dry with materialthe combined extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting product was purified via preparative HPLC-MS (C18
  11. washeluting with a gradient of MeCN and H2O containing 0.15% NH4OH)
  12. customYield (71 mg, 44%)

Sources & evidence

ORD record
ord-043e884e078c4bd5857fd8de6772f6de
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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