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

HRID 628296Notes

Reaction equation

HRID 628296 reaction equation
Cl[C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[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:27]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30].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>[C: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:27]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[NH:28][C:29]([O:31][C:32]([CH3:33])([CH3:34])[CH3:35])=[O:30])=[CH:3][CH:4]=2)[CH:8]=1)=[O:21])([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 85431Di-tert-butyl bicarbamateHCID 118159871tert-butyl 5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-carboxylate

Product 1

HCID 118159681di-tert-butyl 1-[2-(tert-butoxycarbonyl)-1-(phenylsulfonyl)-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

tert-Butyl 5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-carboxylate (0.500 g, 1.27 mmol, from Step 1), di-tert-butyl hydrazine-1,2-dicarboxylate (0.32 g, 1.4 mmol) and Cs2CO3 (0.41 g, 1.3 mmol) were combined in toluene (6 mL) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (0.10 g, 0.13 mmol) was added. The mixture was degassed by a stream of nitrogen through the solution for 10 minutes and was heated to 110° C. for 4 hours. The reaction mixture was cooled to room temperature, partitioned between EtOAc and water, the aqueous phase was extracted a total of three times. The combined extracts were dried over sodium sulfate, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-30% EtOAc in hexanes afforded purified product (0.43 g, 57%).

Workup

  1. customThe mixture was degassed by a stream of nitrogen through the solution for 10 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. custompartitioned between EtOAc and water
  4. extractionthe aqueous phase was extracted a total of three times
  5. dry with materialThe combined extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washFlash chromatography, eluting with a gradient from 0-30% EtOAc in hexanes
  9. customafforded
  10. custompurified product (0.43 g, 57%)

Sources & evidence

ORD record
ord-d13be38df70f4e7796a400492973fea0
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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