Water → HCID 66665461, compound

HRID 872322Notes

Reaction equation

HRID 872322 reaction equation
[C:1]([O:5][C:6](=[O:42])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=C4C=C(B5OC(C)(C)C(C)(C)O5)C=CN4[C:35]=3[C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].Br[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][N:45]=1.O1[CH2:55][CH2:54]OCC1.[OH-].[Na+].O>CN(C=O)C>[C:1]([O:5][C:6](=[O:42])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:44]4[CH:49]=[C:48]([C:55]5[CH:54]=[CH:10][CH:9]=[CH:8][N:7]=5)[CH:47]=[CH:46][N:45]4[C:35]=3[C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 962WaterHCID 79732-BromopyridineHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 66664977HCID 66664977, compound

Product 1

HCID 66665461HCID 66665461, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of (1-{4-[3-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-imidazo[1,2-a]pyridin-2-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl ester [prepared in a manner analogous to that described in Int 11-0; 100% yield assumed] (0.29 mmol) in DMF (3 mL) was added 2-bromopyridine (0.034 mL, 0.32 mmol, 1.1 equiv) and dioxane (1.2 mL). The resulting solution was placed under an argon atmosphere, then, [1,1-bis(diphenylphosphino)ferrocene]dichloro-palladium(II) CH2Cl2 complex (24 mg, 0.03 mmol, 10 mol %) and an aqueous 1 N NaOH solution (0.9 mL, 1.84 mmol, 6.3 equiv) were added. The resulting mixture was heated at 140° C. for 1 h in a microwave apparatus. The resulting mixture was added to water (15 mL). The resulting mixture was extracted with EtOAc (3×25 mL), dried (Na2SO4 anh), and concentrated under reduced pressure. The remaining material was purified using MPLC (Biotage Isolera; 10 g SNAP cartridge: 100% hexane for 2 min., gradient to 70% hexane/30% EtOAc over 1 min., 70% hexane/30% EtOAc for 3 min., gradient to 50% hexane/50% EtOAc over 1.5 min., 50% hexane/50% EtOAc for 2.5 min., gradient to 100% EtOAc over 1 min., 100% EtOAc for 9.6 min,) to give {1-[4-(3-phenyl-7-pyridin-2-yl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (85 mg, 54% two steps):

Workup

  1. extractionThe resulting mixture was extracted with EtOAc (3×25 mL)
  2. dry with materialdried (Na2SO4 anh)
  3. concentrationconcentrated under reduced pressure
  4. customThe remaining material was purified
  5. customMPLC (Biotage Isolera; 10 g SNAP cartridge: 100% hexane for 2 min., gradient to 70% hexane/30% EtOAc over 1 min., 70% hexane/30% EtOAc for 3 min., gradient to 50% hexane/50% EtOAc over 1.5 min., 50% hexane/50% EtOAc for 2.5 min., gradient to 100% EtOAc over 1 min., 100% EtOAc for 9.6 min,)

Sources & evidence

ORD record
ord-68fe163cd175442ea777776713426113
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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