Triethylamine → (+/-)-3-(1-(3-(4-Ethylpyridin-2-yl)-4-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)butanoyl)piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one

HRID 2099756ノート

反応式

HRID 2099756 の反応式
[CH2:1]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH:9]([CH2:14][C:15]2[CH:23]=[C:22]([CH3:24])[C:21]3[C:17](=[CH:18][N:19]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[N:20]=3)[CH:16]=2)[CH2:10][C:11]([OH:13])=O)[CH:4]=1)[CH3:2].N1([C:39]2[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[NH:42][C:41](=[O:49])[N:40]=2)CCCCC1.C(N(CC)CC)C.CCOP(ON1N=[N:75][C:70]2C=[CH:72][CH:73]=[CH:74][C:69]=2C1=O)(OCC)=O>C(Cl)Cl.C(OCC)(=O)C>[CH2:1]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH:9]([CH2:14][C:15]2[CH:23]=[C:22]([CH3:24])[C:21]3[C:17](=[CH:18][N:19]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[N:20]=3)[CH:16]=2)[CH2:10][C:11]([N:75]2[CH2:72][CH2:73][CH:74]([N:40]3[CH2:39][C:48]4[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=4)[NH:42][C:41]3=[O:49])[CH2:69][CH2:70]2)=[O:13])[CH:4]=1)[CH3:2]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 541506284-piperidinyl-2(1H)-quinazolinoneHCID 57794674(+/-)-3-(4-Ethylpyridin-2-yl)-4-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)butanoic Acid

生成物 1

HCID 57794597(+/-)-3-(1-(3-(4-Ethylpyridin-2-yl)-4-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)butanoyl)piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one収率 65%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of (±)-3-(4-ethylpyridin-2-yl)-4-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)butanoic acid (0.166 mmol, 1.0 equiv) in methylene chloride (3 mL) was added 3,4-dihydro-3-(4-piperidinyl-2(1H)-quinazolinone (46 mg, 0.199 mmol, 1.2 equiv). Triethylamine (70 μL) was then added followed by 3-(diethoxyphosphoryloxy)-1,2,3-benzotriain-4(3H)-one (DEPBT, 60 mg, 0.199 mmol 1.2 equiv) under nitrogen. The resulted cloudy yellow solution was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and quenched with 0.5 N sodium hydroxide solution. The layers were separated and the organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography (10% methanol in methylene chloride) to afford the desired product (72 mg, 65% for two steps): (ESI) 667 (MH)+.

後処理

  1. customThe resulted cloudy yellow solution
  2. customquenched with 0.5 N sodium hydroxide solution
  3. customThe layers were separated
  4. washthe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography (10% methanol in methylene chloride)

出典と根拠

ORDレコード
ord-07fc1620c5734c43b0dad20717179d64
出典データセット
uspto-grants-2009_08
特許番号
US07569578B2

反応ノート

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