Potassium Carbonate → 4-(7-(1-methyl-1H-pyrrol-3-yl)-8-(piperidin-4-yloxy)quinazolin-2-ylamino)benzenesulfonamide

HRID 2079622Notes

Reaction equation

HRID 2079622 reaction equation
C([O-])([O-])=O.[K+].[K+].Br[C:8]1[C:17]([O:18][CH:19]2[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]2)=[C:16]2[C:11]([CH:12]=[N:13][C:14]([NH:32][C:33]3[CH:38]=[CH:37][C:36]([S:39](=[O:42])(=[O:41])[NH2:40])=[CH:35][CH:34]=3)=[N:15]2)=[CH:10][CH:9]=1.[CH3:43][N:44]1[CH:48]=[CH:47][C:46](B2OC(C)(C)C(C)(C)O2)=[CH:45]1>COCCOC.[Pd]>[CH3:43][N:44]1[CH:48]=[CH:47][C:46]([C:8]2[C:17]([O:18][CH:19]3[CH2:20][CH2:21][NH:22][CH2:23][CH2:24]3)=[C:16]3[C:11]([CH:12]=[N:13][C:14]([NH:32][C:33]4[CH:34]=[CH:35][C:36]([S:39]([NH2:40])(=[O:41])=[O:42])=[CH:37][CH:38]=4)=[N:15]3)=[CH:10][CH:9]=2)=[CH:45]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 532171481-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrroleHCID 59199265Tert-butyl 4-(7-bromo-2-(4-sulfamoylphenylamino)quinazolin-8-yloxy)piperidine-1-carboxylate

Product 1

HCID 591992634-(7-(1-methyl-1H-pyrrol-3-yl)-8-(piperidin-4-yloxy)quinazolin-2-ylamino)benzenesulfonamideYield 22.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
92.5 °C

Procedure

A 2M solution of K2CO3 (180 μL) was added to a mixture of tert-butyl 4-(7-bromo-2-(4-sulfamoylphenylamino)quinazolin-8-yloxy)piperidine-1-carboxylate (18 mg, 0.031 mmole), 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole (20 mg, 0.093 mmole) and palladium (4 mg, 0.005 mmole) in DME (0.6 mL). The reaction was sparged with argon, sealed and heated at 90-95° C. with stirring. After 90 minutes, LCMS showed that the reaction had reached completion. The Boc group was removed by adding 4M HCl (1.5 mL) in dioxane to the cooled reaction mixture. After 2 hours, the reaction was complete by LCMS. The reaction was filtered, evaporated, dissolved in DMSO (1 mL) and purified by prep. HPLC to give 3.4 mg of the pure product as a TFA salt.

Workup

  1. customThe reaction was sparged with argon
  2. customsealed
  3. customThe Boc group was removed
  4. additionby adding 4M HCl (1.5 mL) in dioxane
  5. customto the cooled reaction mixture
  6. waitAfter 2 hours
  7. filtrationThe reaction was filtered
  8. customevaporated
  9. dissolutiondissolved in DMSO (1 mL)
  10. custompurified by prep

Sources & evidence

ORD record
ord-76489bad23784b35bc2f2a6b0e044c85
Source dataset
uspto-grants-2011_04
Patent number
US07932262B2

Reaction notes

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