Pyridine → HCID 22347011, compound

HRID 898058Notes

Reaction equation

HRID 898058 reaction equation
C(Cl)(=O)C(Cl)=O.[NH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([C:16]([OH:18])=O)=[CH:8]1.[CH3:19][O:20][C:21]1[CH:27]=[C:26]([B:28]2[O:32][C:31]([CH3:34])([CH3:33])[C:30]([CH3:36])([CH3:35])[O:29]2)[CH:25]=[CH:24][C:22]=1[NH2:23].N1C=CC=CC=1>ClCCl.O1CCCC1.CN(C)C=O.C(OCC)(=O)C.O>[CH3:19][O:20][C:21]1[CH:27]=[C:26]([B:28]2[O:29][C:30]([CH3:35])([CH3:36])[C:31]([CH3:34])([CH3:33])[O:32]2)[CH:25]=[CH:24][C:22]=1[NH:23][C:16]([C:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH:7][CH:8]=1)=[O:18]

Participants

10

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 69867Indole-3-Carboxylic AcidHCID 177502072-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Product 1

HCID 22347011HCID 22347011, compoundYield 77.8%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Oxalyl chloride (0.07 mL, 0.79 mmol) was added into a solution of indole-3-carboxylic acid (0.12 g, 0.72 mmol) in dichloromethane (4 mL) and tetrahydrofuran (3 mL) at 0° C. N,N-dimethylforamide (3 drops from 0.1 mL syringe) was added and the mixture was stirred at 0° C. for 10 minutes and at ambient temperature for 20 minutes. The solvents and excess of reagents were evaporated under reduced pressure. The residue was taken into dichloromethane (2 mL) and the resulting solution (1.5 mL) was added into a solution of 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.09 g, 0.36 mmol) and pyridine (1 mL) in dichloromethane (2 mL). The mixture was stirred at ambient temperature overnight. The acid chloride solution in dichloromethane (0.3 mL) was added in and the mixture was stirred overnight. Water (a drop) was added in. The volatile components were evaporated under reduced pressure. The residue was partitioned between water and ethyl acetate. The aqueous layer was separated and extracted with ethyl acetate. The organic extracts were combined and washed with saturated aqueous sodium chloride solution and dried over magnesium sulfate. The mixture was filtered and the solvent of the filtrate was evaporated to yield the crude which was purified by flash column chromatography on silica using n-heptane:ethyl acetate (2/1) as a mobile phase to yield N3-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1H-3-indolecarboxamide (0.11 g, 0.28 mmol) as a white solid: 1H NMR (CDCl3, 400 MHz) δ 8.65 (m, 3H), 8.13 (d, 1H), 7.95 (s, 1H), 7.50 (m, 2H), 7.33(m, 3H), 4.02 (s, 3H), 1.36 (s, 12H); MS: MH+ 393.

Workup

  1. customThe solvents and excess of reagents were evaporated under reduced pressure
  2. stirringThe mixture was stirred at ambient temperature overnight
  3. stirringwas stirred overnight
  4. customThe volatile components were evaporated under reduced pressure
  5. customThe residue was partitioned between water and ethyl acetate
  6. customThe aqueous layer was separated
  7. extractionextracted with ethyl acetate
  8. washwashed with saturated aqueous sodium chloride solution
  9. dry with materialdried over magnesium sulfate
  10. filtrationThe mixture was filtered
  11. customthe solvent of the filtrate was evaporated
  12. customto yield the crude which
  13. customwas purified by flash column chromatography on silica

Sources & evidence

ORD record
ord-377e17e485ab4d65aa89d6aca98228bf
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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