Potassium Carbonate → N-(tert-butyl)-5-(1-chloro-8-phenylpyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamide

HRID 1478401Notes

Reaction equation

HRID 1478401 reaction equation
[Cl:1][C:2]1[C:3]2[N:4]([CH:9]=[CH:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:5](Cl)=[N:6][N:7]=1.[C:18]([NH:22][S:23]([C:26]1[CH:27]=[N:28][CH:29]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:31]=1)(=[O:25])=[O:24])([CH3:21])([CH3:20])[CH3:19].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:18]([NH:22][S:23]([C:26]1[CH:27]=[N:28][CH:29]=[C:30]([C:5]2[N:4]3[CH:9]=[CH:10][C:11]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)=[C:3]3[C:2]([Cl:1])=[N:7][N:6]=2)[CH:31]=1)(=[O:25])=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 90386425N-(tert-Butyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamideHCID 904252191,4-Dichloro-8-phenylpyrrolo[1,2-d][1,2,4]triazine

Product 1

HCID 90425182N-(tert-butyl)-5-(1-chloro-8-phenylpyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamideYield 32%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 1,4-dichloro-8-phenylpyrrolo[1,2-d][1,2,4]triazine (0.150 g, 0.568 mmol) in 1,4-dioxane (15 mL) and water (4 mL) was added N-(tert-butyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamide (prepared according to WO 2011/028741) (0.232 g, 0.682 mmol) followed by potassium carbonate (0.235 g, 1.70 mmol) The reaction mixture was purged with N2 for 30 min. Bis(triphenylphosphine)palladium(II) chloride (20.0 mg, 0.0280 mmol) was added to the reaction mixture and heated at 100° C. in a sealed tube for 12 h. The reaction mixture was allowed to cool and filtered through a pad of CELITE®. The filtrate was concentrated under reduced pressure to give a residue which was suspended in water (100 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure to give a residue which was purified by silica gel column chromatography using CombiFlash (REDISEP®, silica gel, 12 g, 30% EtOAc/hexanes) to yield N-(tert-butyl)-5-(1-chloro-8-phenylpyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamide (80.0 mg, 32.0%) as a pale yellow liquid. LCMS Method B-3: retention time 2.07 min, [M+1]=442.0. 1H NMR (400 MHz, DMSO-d6) δ ppm: 1.19 (s, 9H), 7.23 (d, J=3.2 Hz, 1H), 7.42-7.55 (m, 5H), 7.90 (d, J=3.2 Hz, 1H), 8.00 (br s, 1H), 8.73 (t, J=2.0 Hz, 1H), 9.17 (d, J=2.0 Hz, 1H), 9.22 (d, J=2.0 Hz, 1H).

Workup

  1. customwas purged with N2 for 30 min
  2. temperatureto cool
  3. filtrationfiltered through a pad of CELITE®
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customto give a residue which
  6. extractionextracted with ethyl acetate (3×50 mL)
  7. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  8. customevaporated under reduced pressure
  9. customto give a residue which
  10. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a9218009c5f147a69b6ad5d778f8da4b
Source dataset
uspto-grants-2016_08
Patent number
US09403834B2

Reaction notes

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