Hydrochloric Acid → HCID 66838606、化合物

HRID 2102454ノート

反応式

HRID 2102454 の反応式
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].Br[CH2:31][CH2:32][NH:33]C(=O)OC(C)(C)C.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C(=O)C.CO.O1CCOCC1>[ClH:8].[NH2:33][CH2:32][CH2:31][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]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 4103526tert-Butyl N-(2-bromoethyl)carbamate2 回HCID 136335147HCID 136335147、化合物

生成物 1

HCID 66838606HCID 66838606、化合物収率 170.3%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 312751,4-Dioxane溶媒HCID 31374Dimethylacetamide溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-6775b144cc524e868efbe923be1cffdb
出典データセット
uspto-grants-2009_08
特許番号
US07576074B2

反応ノート

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