Hydrochloric Acid → HCID 66838606, compound

HRID 1752359Notes

Reaction equation

HRID 1752359 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([OH:29])=[C:24]([O:27][CH3:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[Cl:15].[CH3:30][C:31]([N:34](CCBr)C(=O)[O-])(C)C.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C(=O)C.CO.O1CCOCC1>[ClH:8].[NH2:34][CH2:31][CH2:30][O:29][C:23]1[CH:22]=[C:21]2[C:26]([C:17]([NH:16][C:11]3[CH:12]=[CH:13][C:14]([Cl:15])=[C:9]([Cl:8])[CH:10]=3)=[N:18][CH:19]=[N:20]2)=[CH:25][C:24]=1[O:27][CH3:28]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 21081851HCID 21081851, compound2×HCID 136335147HCID 136335147, compound

Product 1

HCID 66838606HCID 66838606, compoundYield 170.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 312751,4-DioxaneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-ol trifluoroacetate (salt) (1.00 g, 2.15 mmol), 1,1-dimethylethyl(2-bromoethyl)carbamate (0.480 g, 2.15 mmol), and potassium carbonate (1.78 g, 12.9 mmol) in N,N-dimethylacetamide (2.2 mL) was heated to 100° C. for 2.5 h. An additional 0.23 g (1.03 mmol) of 1,1-dimethylethyl(2-bromoethyl)carbamate was added and the reaction mixture was further heated to 100° C. for a total of 7 h. The crude reaction mixture was partitioned between water and ethyl acetate and the layers were separated. The aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Column chromatography (SiO2, 3:2 hexanes:acetone) gave N-Boc product, which was then taken up in methanol and treated with 4M hydrogen chloride in dioxane while heating. Dilution with ethyl ether precipitated a pale yellow solid, which was collected by filtration and dried to give 0.761 g (94%) of 7-[(2-aminoethyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine hydrochloride. 1H NMR (400 MHz, d6-DMSO): 12.01 (s, 1H), 8.94 (s, 1H), 8.67 (s, 1H), 8.35 (broad s, 2H), 8.21 (s, 1H), 7.90 (dd, 1H), 7.75 (d, 1H), 7.53 (s, 1H), 4.43 (t, 2H), 4.08 (s, 3H), 3.36 (m, 2H).

Workup

  1. customThe crude reaction mixture
  2. customwas partitioned between water and ethyl acetate
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with ethyl acetate (3×100 mL)
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customColumn chromatography (SiO2, 3:2 hexanes:acetone) gave N-Boc product, which
  9. temperaturewhile heating
  10. customDilution with ethyl ether precipitated a pale yellow solid, which
  11. filtrationwas collected by filtration
  12. customdried

Sources & evidence

ORD record
ord-36e12d53d4df40fea1421d90e842ae22
Source dataset
uspto-grants-2015_10
Patent number
US09163006B2

Reaction notes

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