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

HRID 628366Notes

Reaction equation

HRID 628366 reaction equation
Cl[C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:19]3[N:23]([CH:24]4[CH2:29][CH2:28][CH2:27][CH2:26][O:25]4)[N:22]=[CH:21][CH:20]=3)[N:10]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=3)[C:5]2=[CH:4][CH:3]=1.[NH:30]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].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>[Cl:18][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=1)[CH2:11][N:10]1[C:5]2[C:6](=[N:7][C:2]([N:30]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[NH:31][C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])=[CH:3][CH:4]=2)[CH:8]=[C:9]1[C:19]1[N:23]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)[N:22]=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonate2×HCID 85431Di-tert-butyl bicarbamate2×HCID 1181596805-chloro-1-(3-chlorobenzyl)-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]-1H-pyrrolo[3,2-b]pyridine

Product 1

HCID 118159899di-tert-butyl 1-{1-(3-chlorobenzyl)-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]-1H-pyrrolo[3,2-b]pyridin-5-yl}hydrazine-1,2-dicarboxylate

Reagents, catalysts & solvents 2

HCID 178439015HCID 178439015, compoundCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

5-Chloro-1-(3-chlorobenzyl)-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]-1H-pyrrolo[3,2-b]pyridine (0.87 g, 1.8 mmol, from Step 3), di-tert-butyl hydrazine-1,2-dicarboxylate (0.64 g, 2.7 mmol, Aldrich) and Cs2CO3 (0.90 g, 2.7 mmol, Aldrich) were combined in toluene (16 mL) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (0.14 g, 0.18 mmol, Aldrich) was added. The mixture was degassed by a stream of nitrogen through the solution for 10 minutes. The reaction was heated in a sealed vial to 130° C. for 55 minutes, then at 135° C. for 40 minutes. Additional di-tert-butyl hydrazine-1,2-dicarboxylate (0.32 g, 1.4 mmol), Cs2CO3 (0.45 g, 1.4 mmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (0.10 g, 0.13 mmol) were added. The mixture was again degassed, then sealed and heated to 140° C. for 40 minutes. After cooling to room temperature, the mixture was diluted with DCM, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-50% EtOAc in hexanes afforded product as a white solid (0.51 g, 40%). LCMS (M+H)+: 623.3.

Workup

  1. customThe mixture was degassed by a stream of nitrogen through the solution for 10 minutes
  2. customThe mixture was again degassed
  3. customsealed
  4. temperatureheated to 140° C. for 40 minutes
  5. temperatureAfter cooling to room temperature
  6. additionthe mixture was diluted with DCM
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washFlash chromatography, eluting with a gradient from 0-50% EtOAc in hexanes afforded product as a white solid (0.51 g, 40%)

Sources & evidence

ORD record
ord-a68458fe87d643299c8b261720f1f445
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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