Lithium Chloride → HCID 67055891, compound

HRID 2036854Notes

Reaction equation

HRID 2036854 reaction equation
Br[C:2]1[S:6][C:5]([S:7]([NH:10][C:11]([CH3:14])([CH3:13])[CH3:12])(=[O:9])=[O:8])=[N:4][CH:3]=1.[Cl-].[Li+].C[Sn](C)C.C[Sn](C)C.Cl[C:26]1[N:35]=[C:34]([NH:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=2)[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][C:32]=2[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[N:27]=1>O1CCOCC1>[C:11]([NH:10][S:7]([C:5]1[S:6][C:2]([C:26]2[N:35]=[C:34]([NH:36][CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=3)[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][C:32]=3[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[N:27]=2)=[CH:3][N:4]=1)(=[O:9])=[O:8])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 433294Lithium ChlorideHCID 6327618HexamethylditinHCID 67055896HCID 67055896, compoundHCID 866706132-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine

Product 1

HCID 67055891HCID 67055891, compoundYield 4.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
90 °C

Procedure

To a stirring suspension of 5-bromo-N-tert-butylthiazole-2-sulfonamide (0.50 g, 1.67 mmol) in 1,4-dioxane (10 mL) was added lithium chloride (0.210 g, 5.03 mmol), followed by hexamethylditin (0.820 g, 2.50 mmol). After degassing with nitrogen, Pd(TPP)4 (0.19 g, 0.16 mmol) was added. The resultant suspension was stirred for over night at RT. 2-Chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine (0.46 g, 1.33 mmol) was dissolved in 1,4-dioxane (3 mL) and then added to the reaction mixture. Upon completion of addition, the reaction mixture was heated at 90° C. for 24 h. After this time, the solvent was evaporated, water was added and the mixture was extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated. The resulting residue was purified by recrystallization with ethyl acetate and further purified by preparative HPLC (method H) to provide N-tert-butyl-5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)thiazole-2-sulfonamide (32 mg, 4.2%) as a yellow solid. LCMS Method V: Rt 2.47 min; [M+1]=531.2; HPLC Method A1: purity 97.3%, retention time=10.89 min.

Workup

  1. additionwas added
  2. additionadded to the reaction mixture
  3. additionUpon completion of addition
  4. customAfter this time, the solvent was evaporated
  5. additionwater was added
  6. extractionthe mixture was extracted with DCM
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by recrystallization with ethyl acetate
  11. customfurther purified by preparative HPLC (method H)

Sources & evidence

ORD record
ord-b8c4d854131149be87b3c4fc16588546
Source dataset
uspto-grants-2013_11
Patent number
US08575184B2

Reaction notes

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