Acetaldehyde → N-(3,4-dichlorophenyl)-7-{[(5-ethyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine hydrochloride

HRID 2102480노트

반응식

HRID 2102480 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][C:24]4[S:25][C:26]5[CH2:27][NH:28][CH2:29][CH2:30][C:31]=5[N:32]=4)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH:33](=O)[CH3:34].[BH3-]C#N.[Na+].CO.C(OCC)(=O)C>C1COCC1.CO>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][C:24]4[S:25][C:26]5[CH2:27][N:28]([CH2:33][CH3:34])[CH2:29][CH2:30][C:31]=5[N:32]=4)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]

참가 물질

6

반응물 4

HCID 177Acetaldehyde3회HCID 5003444Sodium cyanoborohydride3회HCID 21584119Ethylacetate methanolHCID 53630967N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-ylmethyl)oxy]quinazolin-4-amine

생성물 1

HCID 66838644N-(3,4-dichlorophenyl)-7-{[(5-ethyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine hydrochloride수율 25.5%

시약·촉매·용매 1

HCID 21899815MeOH tetrahydrofuran용매

실험 절차

N-(3,4-Dichlorophenyl)-6-(methyloxy)-7-[(4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-ylmethyl)oxy]quinazolin-4-amine (0.249 g, 0.510 mmol) was taken up in 50% THF/MeOH (10 mL) and the solution was cooled with an ice bath. Acetaldehyde (0.057 mL, 1.0 mmol), followed by NaCNBH3 (0.038 g, 0.61 mmol) were added. The solution was allowed to warm to room temperature. After 4 h, additional acetaldehyde (0.050 mL, 0.89 mmol) and NaCNBH3 (0.040 g, 0.64 mmol) were added and the solution was stirred for 12 h. An additional 0.050 mL (0.89 mmol) of acetaldehyde and NaCNBH3 (0.020 g, 0.32 mmol) were added. The solution was poured into 10% MeOH/ethyl acetate (100 mL) and washed once with H2O (100 mL). The organic layer was dried (Na2SO4); filtered and the solvent was removed in vacuo. The crude product was purified via preparative HPLC (reverse phase, CH3CN/H2O/NH4OAc/AcOH). The solvents were removed, the product was taken up in MeOH and treated with 4.0M HCl/dioxane (0.025 mL), and lyophilized to provide 0.036 g (12%) of N-(3,4-dichlorophenyl)-7-{[(5-ethyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine hydrochloride as a yellow solid.

후처리

  1. temperaturethe solution was cooled with an ice bath
  2. additionwere added
  3. washwashed once with H2O (100 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo
  7. customThe crude product was purified via preparative HPLC (reverse phase, CH3CN/H2O/NH4OAc/AcOH)
  8. customThe solvents were removed
  9. additiontreated with 4.0M HCl/dioxane (0.025 mL)

출처 및 근거

ORD 기록
ord-0ddba856609a4b109c82740796767510
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07576074B2

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