Potassium Carbonate → (S)-tert-Butyl 2-(4-chlorophenyl)-3-oxo-3-(4-(5-phenyl-1H-pyrrolo[2,3-b]pyri din-4-yl)piperazin-1-yl)propyl(isopropyl)carbamate

HRID 79546Notes

Reaction equation

HRID 79546 reaction equation
Br[C:2]1[C:3]([N:11]2[CH2:16][CH2:15][N:14]([C:17](=[O:38])[C@@H:18]([C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=3)[CH2:19][N:20]([CH:28]([CH3:30])[CH3:29])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:13][CH2:12]2)=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[C:39]1(B(O)O)[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=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:37][C:34]1[CH:35]=[CH:36][C:31]([C@H:18]([C:17](=[O:38])[N:14]2[CH2:15][CH2:16][N:11]([C:3]3[C:2]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)=[CH:7][N:6]=[C:5]4[NH:8][CH:9]=[CH:10][C:4]=34)[CH2:12][CH2:13]2)[CH2:19][N:20]([CH:28]([CH3:30])[CH3:29])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[CH:32][CH:33]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 68764847(5)-Tert-butyl 3-(4-(5-bromo-1h-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)-2-(4-chlorophenyl)-3-oxopropyl(isopropyl)carbamate

Product 1

HCID 68764607(S)-tert-Butyl 2-(4-chlorophenyl)-3-oxo-3-(4-(5-phenyl-1H-pyrrolo[2,3-b]pyri din-4-yl)piperazin-1-yl)propyl(isopropyl)carbamateYield 2%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

(S)-tert-Butyl 3-(4-(5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-2-(4-chlorophenyl)-3-oxopropyl(isopropyl)carbamate (0.150 g, 0.248 mmol, see Example 4), phenylboronic acid (0.0363 g, 0.298 mmol), Pd(PPh3)4 (0.0143 g, 0.0124 mmol) and 10% K2CO3 (aq., 0.517 mL, 0.372 mmol) were placed in Ar degassed 2:1 toluene:EtOH and heated to 80° C. overnight. The reaction was cooled to room temperature, diluted with water, and extracted with DCM. The combined organic fractions were dried, filtered, concentrated, and purified (500:7 DCM:MeOH) to give (S)-tert-butyl 2-(4-chlorophenyl)-3-oxo-3-(4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)propyl(isopropyl)carbamate (0.003 g, 2.0% yield)

Workup

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

Sources & evidence

ORD record
ord-60761eaabe224e6da7dab2c4aa31720f
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

Loading…