Potassium Carbonate → (R)-tert-butyl 3-(4-chlorophenyl)-1-oxo-1-(4-(5-phenyl-1H-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)propan-2-ylcarbamate

HRID 79538Notes

Reaction equation

HRID 79538 reaction equation
Br[C:2]1[C:3]([N:11]2[CH2:16][CH2:15][N:14]([C:17](=[O:35])[C@H:18]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[CH2:13][CH2:12]2)=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[C:36]1(B(O)O)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C([O-])([O-])=O.[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:26][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][C@@H:18]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33])[C:17](=[O:35])[N:14]2[CH2:15][CH2:16][N:11]([C:3]3[C:2]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[CH:7][N:6]=[C:5]4[NH:8][CH:9]=[CH:10][C:4]=34)[CH2:12][CH2:13]2)=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 68763825(R)-tert-Butyl 1-(4-(5-bromo-1H-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)-3-(4-chlorophenyl)-1-oxopropan-2-ylcarbamate

Product 1

HCID 68761687(R)-tert-butyl 3-(4-chlorophenyl)-1-oxo-1-(4-(5-phenyl-1H-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)propan-2-ylcarbamateYield 10%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

(R)-tert-Butyl 1-(4-(5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-3-(4-chlorophenyl)-1-oxopropan-2-ylcarbamate (0.180 g, 0.320 mmol, see Example 1), phenylboronic acid (0.0468 g, 0.384 mmol), Pd(PPh3)4 (0.0185 g, 0.0160 mmol) and 10% K2CO3 (aq., 0.66 mL, 0.47 mmol) were added to an Ar degassed solution of 2:1 toluene:EtOH (3 mL). The reaction was then heated to 80° C. overnight. The reaction was then cooled to room temperature, diluted with water, and extracted with DCM. The organic fractions were dried, filtered, concentrated, and purified (500:10-500:15) to give (R)-tert-butyl 3-(4-chlorophenyl)-1-oxo-1-(4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)propan-2-ylcarbamate (0.018 g, 10.0% yield).

Workup

  1. customdegassed solution of 2:1 toluene
  2. temperatureThe reaction was then cooled to room temperature
  3. additiondiluted with water
  4. extractionextracted with DCM
  5. customThe organic fractions were dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified (500:10-500:15)

Sources & evidence

ORD record
ord-4c862b85839c402c9f84e0afe6424c93
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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