Hydrochloric Acid → HCID 67298218, compound

HRID 1520381Notes

Reaction equation

HRID 1520381 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[N:8]=[C:7]([C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)[N:6]=[C:5]2[NH:19][CH3:20].[F:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1.[ClH:31]>O1CCOCC1.O.C(O)C.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>[ClH:31].[ClH:31].[F:21][C:22]1[CH:27]=[C:26]([C:2]2[CH:3]=[C:4]3[C:9](=[C:10]([CH3:12])[CH:11]=2)[N:8]=[C:7]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[N:6]=[C:5]3[NH:19][CH3:20])[CH:25]=[CH:24][CH:23]=1

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 27339863-Fluorophenylboronic acidHCID 71268873HCID 71268873, compound

Product 1

HCID 67298218HCID 67298218, compoundYield 71%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

6-Bromo-N,8-dimethyl-2-(pyridin-3-yl)quinazolin-4-amine (340 mg, 1.03 mmol), 3-fluorobenzeneboronic acid (217 mg, 1.55 mmol), K2PO4 (658 mg, 3.10 mmol) and Pd(PPh3)4 (59.7 mg, 0.052 mmol) were dissolved in the mixed solvent of 1,4-dioxane (10 mL) and water (1 mL). The resulting mixture was stirred at 90° C. for 6 hours under a nitrogen atmosphere. After the reaction was completed, water was added to the mixture and stirred for 30 minutes. The resulting precipitate was collected by filtration and purified by column chromatography on NH-silica gel (eluted with THF) to give a yellow powder. The solid was suspended in ethanol and 5N HCl (1 mL) was added to the mixture. The mixture was sonicated for 10 min and the resulting precipitate was collected by filtration and dried to give 304 mg of 6-(3-fluorophenyl)-N,8-dimethyl-2-(pyridin-3-yl)quinazolin-4 amine dihydrochloride as a yellow powder in 71% yield.

Workup

  1. stirringstirred for 30 minutes
  2. filtrationThe resulting precipitate was collected by filtration
  3. custompurified by column chromatography on NH-silica gel (eluted with THF)
  4. customto give a yellow powder
  5. customThe mixture was sonicated for 10 min
  6. filtrationthe resulting precipitate was collected by filtration
  7. customdried

Sources & evidence

ORD record
ord-06bdfc9c15204a4db987011aba02db21
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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