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 1752385ノート

反応式

HRID 1752385 の反応式
[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]

参加物

6

反応物 4

HCID 177Acetaldehyde3 回HCID 5003444Sodium cyanoborohydride3 回HCID 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

生成物 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 hydrochloride収率 25.5%

試薬・触媒・溶媒 1

HCID 21899815MeOH tetrahydrofuran溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-83dd2362ca244ae7838df35822fac484
出典データセット
uspto-grants-2015_10
特許番号
US09163006B2

反応ノート

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