Nitrogen → 5-chloro-4-((5-chloro-6-cyclopropylpyridin-3-yl)methyl)-2-fluoro-N-(methylsulfonyl)benzamide

HRID 2048022Notes

Reaction equation

HRID 2048022 reaction equation
[Cl:1][C:2]1[C:3]([CH:17]2[CH2:19][CH2:18]2)=[N:4][CH:5]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:7]=1.Br[CH2:21][C:22]1[C:34]([Cl:35])=[CH:33][C:25]([C:26]([NH:28][S:29]([CH3:32])(=[O:31])=[O:30])=[O:27])=[C:24]([F:36])[CH:23]=1.C(=O)([O-])[O-].[K+].[K+].N#N>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.O.O1CCCC1>[Cl:35][C:34]1[C:22]([CH2:21][C:6]2[CH:5]=[N:4][C:3]([CH:17]3[CH2:18][CH2:19]3)=[C:2]([Cl:1])[CH:7]=2)=[CH:23][C:24]([F:36])=[C:25]([CH:33]=1)[C:26]([NH:28][S:29]([CH3:32])(=[O:31])=[O:30])=[O:27]

Participants

8

Reactant 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 58042381(5-Chloro-6-cyclopropylpyridin-3-yl)boronic acid pinacol esterHCID 580423974-(bromomethyl)-5-chloro-2-fluoro-N-(methylsulfonyl)benzamide

Product 1

HCID 580425025-chloro-4-((5-chloro-6-cyclopropylpyridin-3-yl)methyl)-2-fluoro-N-(methylsulfonyl)benzamide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of tetrahydrofuran (10 mL) and water (2 mL) was added 3-chloro-2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (Preparation 221, 32 mg, 0.11 mmol), 4-(bromomethyl)-5-chloro-2-fluoro-N-(methylsulfonyl)benzamide (Preparation 243, 43 mg, 0.13 mmol) and potassium carbonate (46 mg, 0.35 mmol). The flask was degassed with N2 (×5), and tetrakistriphenylphosphinepalladium (13.2 mg, 0.01 mmol) was added. The flask was degassed with N2 (×5), and heated to 65° C. for 18 hours. The reaction was allowed to cool to room temperature and washed with a saturated aqueous solution of ammonium chloride (100 mL). The reaction was extracted into ethyl acetate (3×50 mL). The combined organic layers were dried over MgSO4, filtered and the solvent removed to leave a yellow oil. The material was purified by silica gel column chromatography eluting with 1:1 heptane:ethyl acetate to afford the title compound as a yellow oil that solidified to a pale yellow solid upon standing (23 mg, 48%).

Workup

  1. additionwas added
  2. customThe flask was degassed with N2 (×5)
  3. temperatureto cool to room temperature
  4. washwashed with a saturated aqueous solution of ammonium chloride (100 mL)
  5. extractionThe reaction was extracted into ethyl acetate (3×50 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. customthe solvent removed
  9. customto leave a yellow oil
  10. customThe material was purified by silica gel column chromatography
  11. washeluting with 1:1 heptane

Sources & evidence

ORD record
ord-3a1a5c8b77f748c09ab3820a02416968
Source dataset
uspto-grants-2013_11
Patent number
US08592629B2

Reaction notes

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