Toluene → HCID 118159647, compound

HRID 628376Notes

Reaction equation

HRID 628376 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[N:12][C:13](Cl)=[CH:14][CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:18]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].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:18]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[NH:19][C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])=[CH:14][CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 85431Di-tert-butyl bicarbamateHCID 118159700HCID 118159700, compound

Product 1

HCID 118159647HCID 118159647, compound

Reagents, catalysts & solvents 1

HCID 178439015HCID 178439015, compoundCatalyst

Conditions

Temperature
110 °C

Procedure

A reaction vial was charged with 1-benzyl-5-chloro-1H-pyrazolo[4,3-b]pyridine (0.210 g, 0.862 mmol) (Peak 1 from Step 1), di-tert-butyl hydrazine-1,2-dicarboxylate (0.22 g, 0.96 mmol, Aldrich), cesium carbonate (0.281 g, 0.862 mmol, Aldrich) and toluene (2 mL, 20 mmol). Dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (0.068 g, 0.086 mmol, Aldrich) was added and the mixture was degassed by a stream of nitrogen through the solution for 15 minutes. The reaction vial was sealed and heated to 110° C. for 2 hours, then was stirred at room temperature for 3 days. The reaction mixture was partitioned between ethyl acetate and water and the aqueous was extracted with two further portions of EtOAc. The combined extracts were dried over sodium sulfate, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-50% EtOAc in hexanes afforded product (0.19 g, 50%).

Workup

  1. customA reaction
  2. customthe mixture was degassed by a stream of nitrogen through the solution for 15 minutes
  3. customThe reaction
  4. customvial was sealed
  5. customThe reaction mixture was partitioned between ethyl acetate and water
  6. extractionthe aqueous was extracted with two further portions of EtOAc
  7. dry with materialThe combined extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washFlash chromatography, eluting with a gradient from 0-50% EtOAc in hexanes afforded product (0.19 g, 50%)

Sources & evidence

ORD record
ord-f42cf4a8a48e461fbd86bb2773b77940
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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