Triethylamine → 4-(2-Oxo-1,4-dihydro-2h-quinazolin-3-yl)-piperidine-1-carboxylic acid[1-(6-benzyloxy-pyridin-3-ylmethyl)-2-[1,4']bipiperidinyl-1'-yl-2-oxo-ethyl]-amide

HRID 1353578ノート

反応式

HRID 1353578 の反応式
CO[C:3](=[O:40])[CH:4]([NH:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([N:29]2[CH2:38][C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[NH:31][C:30]2=[O:39])[CH2:25][CH2:24]1)=[O:22])[CH2:5][C:6]1[CH:7]=[N:8][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH:11]=1.O.[OH-].[Li+].[N:44]1([CH:50]2[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]2)[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]1.C(N(CC)CC)C.[PH2](Cl)=O>CO.O>[CH2:13]([O:12][C:9]1[N:8]=[CH:7][C:6]([CH2:5][CH:4]([NH:20][C:21]([N:23]2[CH2:24][CH2:25][CH:26]([N:29]3[CH2:38][C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[NH:31][C:30]3=[O:39])[CH2:27][CH2:28]2)=[O:22])[C:3]([N:53]2[CH2:54][CH2:55][CH:50]([N:44]3[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]3)[CH2:51][CH2:52]2)=[O:40])=[CH:11][CH:10]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

参加物

8

反応物 5

HCID 8471TriethylamineHCID 786071,4'-BipiperidineHCID 168937Lithium hydroxide, monohydrateHCID 588642363-(6-benzyloxy-pyridin-3-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl esterHCID 178527016HCID 178527016、化合物

生成物 1

HCID 100097694-(2-Oxo-1,4-dihydro-2h-quinazolin-3-yl)-piperidine-1-carboxylic acid[1-(6-benzyloxy-pyridin-3-ylmethyl)-2-[1,4']bipiperidinyl-1'-yl-2-oxo-ethyl]-amide

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 962Water溶媒

実験手順

To a stirred solution of 3-(6-benzyloxy-pyridin-3-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl ester (59 mg, 0.11 mmol) in methanol (3 mL) was added a solution of lithium hydroxide monohydrate (9.1 mg, 2 equiv) in water (0.5 mL). The reaction was stirred 2 h at room temperature, cooled to 0° C., quenched by addition of 1N hydrochloric acid (0.15 mL), and concentrated. The crude product was used without purification. The crude acid was dissolved in methylene chloride (2 mL, 0° C.), and treated sequentially with 4-piperidino-piperidine (34 mg, 1.8 equiv), triethylamine (35 μL, 2.3 equiv.), and bis-2-oxo-3-oxazolidinyl)phoshinic chloride (34 mg, 1.2 equiv). The ice bath was removed and the reaction allowed to stir overnight. The reaction was concentrated and purified by Prep TLC to give 30.3 mg (41%). LC/MS: tR=1.49 min, 680.29 (MH)+.

後処理

  1. temperaturecooled to 0° C.
  2. customquenched by addition of 1N hydrochloric acid (0.15 mL)
  3. concentrationconcentrated
  4. customThe crude product was used without purification
  5. dissolutionThe crude acid was dissolved in methylene chloride (2 mL, 0° C.)
  6. customThe ice bath was removed
  7. stirringto stir overnight
  8. concentrationThe reaction was concentrated
  9. custompurified by Prep TLC
  10. customto give 30.3 mg (41%)

出典と根拠

ORDレコード
ord-9a857c728b9744458048fdbc8d607d6d
出典データセット
uspto-grants-2007_05
特許番号
US07220862B2

反応ノート

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