M-Phenylenediamine → HCID 18925092, compound

HRID 1869077Notes

Reaction equation

HRID 1869077 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[C:16]1([NH2:23])[CH:21]=[CH:20][CH:19]=[C:18]([NH2:22])[CH:17]=1>C(O)(C)C>[ClH:1].[NH2:22][C:18]1[CH:17]=[C:16]([NH:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)[CH:21]=[CH:20][CH:19]=1

Participants

4

Reactant 2

HCID 7935M-PhenylenediamineHCID 27693644-Chloro-6,7-dimethoxyquinazoline

Product 1

HCID 18925092HCID 18925092, compoundYield 93.9%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
20 °C

Procedure

4-Chloro-6,7-dimethoxyquinazoline (5.01 g, 22.3 mmol) was added in portions, over 1.5 hours, to m-phenylenediamine (2.66 g, 24.6 mmol) in refluxing isopropanol (100 mL) under an atmosphere of dry nitrogen. After the addition was complete the mixture was heated at reflux for 4 hours. The mixture was cooled to 20° C., and the precipitate was filtered, washed with chilled isopropanol and dried in vacuo to afford 6.97 g (93%) of (3-aminophenyl)-(6,7-dimethoxyquinazolin-4-yl)amine hydrochloride (LC-MS: 297 (MH+). To a solution of the above product (50 mg, 0.169 mmol) in 80% acetic acid/H2O (2 mL), at 0° C., was added a solution of NaNO2 (18.4 mg, 0.186 mmol) in H2O (100 μL). After stirring 10 minutes at 0° C. a solution of NaN3 (12 mg, 0.185 mmol) in H2O (100 μL) was added. The mixture was allowed to warm to 20° C. and stirred for 1.5 hours. The reaction mixture was lyophilized and the residue partitioned between ethyl acetate and saturated aqueous NaHCO3. The organic phase was wahsed further with brine, dried over Na2SO4, filtered, and concentrated, in vacuo. Recrystallization from CHCl3/hexanes afforded 36 mg of the title product as a white solid; mp 110°-113° C.

Workup

  1. additionAfter the addition
  2. temperaturewas heated
  3. temperatureat reflux for 4 hours
  4. filtrationthe precipitate was filtered
  5. washwashed with chilled isopropanol
  6. customdried in vacuo

Sources & evidence

ORD record
ord-581c1827cdf5401baa720277f49ed30d
Source dataset
uspto-grants-2009_12
Patent number
USRE041065E1

Reaction notes

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