Water → {1-[4-(3-Phenyl-7-vinyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 872324Notes

Reaction equation

HRID 872324 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[CH:25]=[C:24](Br)[CH:23]=[CH:22][N:21]4[C:27]=3[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].O.CO[CH2:44][CH2:45]OC>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[CH:25]=[C:24]([CH:44]=[CH2:45])[CH:23]=[CH:22][N:21]4[C:27]=3[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 66665545{1-[4-(7-Bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Product 1

HCID 66665226{1-[4-(3-Phenyl-7-vinyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterYield 85%

Reagents, catalysts & solvents 1

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Procedure

A mixture of {1-[4-(7-bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (100 mg, 0.19 mmol) and tetrakis(triphenylphosphine)-palladium(0) (2.2 mg, 0.2 mmol, 1.0 mol %) in DME (1.5 mL) under an atmosphere of argon was stirred at room temperature for 10 min. To the resulting mixture was added K2CO3 (26.7 mg, 0.19 mmol, 1.0 equiv) and water (0.5 mL), followed by 2,4,6-trivinyl-cyclotriboroxane pyridine complex (46.4 mg, 0.19 mmol, 1 equiv). The resulting mixture was heated at the reflux temperature for 16 h with monitoring by UPLC-MS. The resulting mixture was concentrated under reduced pressure and treated with water (10 mL). The resulting mixture was extracted with EtOAc (2×10 mL). The combined organic phases were washed with water (10 mL), dried (Na2SO4 anh), and concentrated under reduced pressure. The remaining material was purified using MPLC (Biotage Isolera Flash NH2 Snap 10 reverse phase column; 99% CH2Cl2/1% MeOH for 1 min., gradient to 90% CH2Cl2/10% MeOH over 10 min.; 90% CH2Cl2/10% MeOH over 5.2 min.) to give {1-[4-(3-phenyl-7-vinyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (77 mg, 85%),:

Workup

  1. temperatureThe resulting mixture was heated at the reflux temperature for 16 h with monitoring by UPLC-MS
  2. concentrationThe resulting mixture was concentrated under reduced pressure
  3. additiontreated with water (10 mL)
  4. extractionThe resulting mixture was extracted with EtOAc (2×10 mL)
  5. washThe combined organic phases were washed with water (10 mL)
  6. dry with materialdried (Na2SO4 anh)
  7. concentrationconcentrated under reduced pressure
  8. customThe remaining material was purified
  9. wait99% CH2Cl2/1% MeOH for 1 min.
  10. waitgradient to 90% CH2Cl2/10% MeOH over 10 min.

Sources & evidence

ORD record
ord-9114f309845c472b82cbe325deecfa3a
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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