Hydrochloric Acid → HCID 66838606, 화합물

HRID 1752359노트

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HRID 1752359 반응식
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]

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 21081851HCID 21081851, 화합물2회HCID 136335147HCID 136335147, 화합물

생성물 1

HCID 66838606HCID 66838606, 화합물수율 170.3%

시약·촉매·용매 3

HCID 887Methanol용매HCID 312751,4-Dioxane용매HCID 31374Dimethylacetamide용매

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온도
100 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-36e12d53d4df40fea1421d90e842ae22
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09163006B2

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