Toluene → di-tert-butyl 1-[2-(ethoxycarbonyl)-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridin-5-yl]hydrazine-1,2-dicarboxylate

HRID 628335Notes

Reaction equation

HRID 628335 reaction equation
Cl[C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[N:10]([S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:5]2=[CH:4][CH:3]=1.[NH:25]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].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>[CH2:23]([O:22][C:20]([C:9]1[N:10]([S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])[C:5]2[C:6](=[N:7][C:2]([N:25]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[NH:26][C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])=[CH:3][CH:4]=2)[CH:8]=1)=[O:21])[CH3:24]

Participants

6

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 85431Di-tert-butyl bicarbamateHCID 53816579Ethyl 1-(benzenesulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carboxylate

Product 1

HCID 118159434di-tert-butyl 1-[2-(ethoxycarbonyl)-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridin-5-yl]hydrazine-1,2-dicarboxylate

Reagents, catalysts & solvents 1

HCID 178439015HCID 178439015, compoundCatalyst

Conditions

Temperature
110 °C

Procedure

Ethyl 5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-carboxylate (1.80 g, 4.93 mmol, from Step 1), di-tert-butyl hydrazine-1,2-dicarboxylate (1.3 g, 5.4 mmol, Aldrich) and Cs2CO3 (1.6 g, 4.9 mmol, Aldrich) were combined in toluene (20 mL, 200 mmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (0.39 g, 0.49 mmol, Aldrich) was added. The mixture was degassed by a stream of nitrogen through the solution for 10 minutes. The reaction was stirred at 110° C. for 3.5 hours. The reaction was cooled to room temperature, water was added and the product was extracted with five 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 as a yellow foam (2.11 g, 76%).

Workup

  1. customThe mixture was degassed by a stream of nitrogen through the solution for 10 minutes
  2. temperatureThe reaction was cooled to room temperature
  3. additionwater was added
  4. extractionthe product was extracted with five portions of EtOAc
  5. dry with materialThe combined extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washFlash chromatography, eluting with a gradient from 0-50% EtOAc in hexanes afforded product as a yellow foam (2.11 g, 76%)

Sources & evidence

ORD record
ord-682bccd4a9b24bd0bb6ca2136feb03fa
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

Loading…