Potassium Phosphate, Tribasic → {1-[4-(7-Cyclopropyl-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 872321Notes

Reaction equation

HRID 872321 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].[CH:35]1(B(O)O)[CH2:37][CH2:36]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.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>[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:35]5[CH2:37][CH2:36]5)[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 3

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 66665545{1-[4-(7-Bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Product 1

HCID 66665748{1-[4-(7-Cyclopropyl-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterYield 88.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of {1-[4-(7-bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (200 mg, 0.38 mmol), cyclopropylboronic acid (166 mg, 1.93 mmol, 5.0 equiv), tetrakis(triphenylphosphine)palladium(0) (18 mg, 0.015 mmol, 4 mol %) and K3PO4 (164 mg, 0.77 mmol, 2.0 equiv), in toluene (4.5 mL) was heated at the reflux temperature for 16 h with monitoring by UPLC-MS. The resulting mixture was heated at 90° C. for 1 h in a microwave apparatus, then concentrated under reduced pressure. The remaining material was treated with water (25 mL), and was then extracted with EtOAc (2×25 mL). The combined organic phases were washed with water (25 mL), dried (Na2SO4 anh), and concentrated under reduced pressure. The remaining material (205 mg) was was purified using MPLC (Biotage Isolera Flash NH2 Snap 10 reverse phase column; 100% CH2Cl2 for 1 min., gradient to 90% CH2Cl2/10% MeOH over 10 min.; 90% CH2Cl2/10% MeOH for 4 min.) to give {1-[4-(7-cyclopropyl-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (162 mg, 87%):

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe remaining material was treated with water (25 mL)
  3. extractionwas then extracted with EtOAc (2×25 mL)
  4. washThe combined organic phases were washed with water (25 mL)
  5. dry with materialdried (Na2SO4 anh)
  6. concentrationconcentrated under reduced pressure
  7. customThe remaining material (205 mg) was was purified
  8. waitgradient to 90% CH2Cl2/10% MeOH over 10 min.

Sources & evidence

ORD record
ord-fdcdc1d9b445410c9041ecc65b5841e2
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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