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Diisopropylethylamine → (2-{1-[2,6-Bis-(4-cyano-phenoxy)-pyridine-3-carbonyl]-piperidin-4-yl}-ethyl)-carbamic Acid Tert-butyl Ester

HRID 1024681
ノート
印刷プレビュー

反応式

HRID 1024681 の反応式
[C:1]([C:3]1[CH:27]=[CH:26][C:6]([O:7][C:8]2[N:16]=[C:15]([O:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=3)[CH:14]=[CH:13][C:9]=2[C:10](O)=[O:11])=[CH:5][CH:4]=1)#[N:2].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[C:70]([O:74][C:75](=[O:85])[NH:76][CH2:77][CH2:78][CH:79]1[CH2:84][CH2:83][NH:82][CH2:81][CH2:80]1)([CH3:73])([CH3:72])[CH3:71]>CN(C=O)C>[C:70]([O:74][C:75](=[O:85])[NH:76][CH2:77][CH2:78][CH:79]1[CH2:80][CH2:81][N:82]([C:10]([C:9]2[C:8]([O:7][C:6]3[CH:26]=[CH:27][C:3]([C:1]#[N:2])=[CH:4][CH:5]=3)=[N:16][C:15]([O:17][C:18]3[CH:19]=[CH:20][C:21]([C:24]#[N:25])=[CH:22][CH:23]=3)=[CH:14][CH:13]=2)=[O:11])[CH2:83][CH2:84]1)([CH3:73])([CH3:71])[CH3:72]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 15018494-(2-Aminoethyl)piperidine, 4-BOC protectedHCID 2724699PyBOPHCID 676059982,6-Bis(4-cyanophenoxy)-nicotinic acid

生成物 1

HCID 66818540(2-{1-[2,6-Bis-(4-cyano-phenoxy)-pyridine-3-carbonyl]-piperidin-4-yl}-ethyl)-carbamic Acid Tert-butyl Ester

試薬・触媒・溶媒 1

HCID 6228
Dimethylformamide
溶媒
3 回

実験手順

A solution of 2,6-Bis-(4-cyano phenoxy)-nicotinic acid, 0.335 g (0.94 mmol), in 5 ml of DMF was added dropwise to the stirred suspension of 0.489 g (0.94 mmol) of benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBop) in 5 ml of DMF and followed by N,N-diisopropylethylamine 0.242 g (1.88 mmol) while the temperature was maintained below 5° C. during the addition. The mixture was stirred for 10 min and a solution of (2-piperidin-4-yl-ethyl)-carbamic acid tert-butyl ester (0.214 g, 0.94 mmol) in 2 ml of DMF was added. The mixture was stirred overnight at RT. The solvent was concentrated under reduced pressure and the residue was dissolved in a mixture of water (150 ml) and ethyl acetate (150 ml). The pH was adjusted to 2-3 with 6 N HCl and the phases were separated. The aqueous phase was extracted with ethyl acetate. The combined organic phase was washed with 10% solution of potassium hydrogen sulphate followed by saturated sodium bicarbonate solutiona and saturated brine solution, and dried over sodium sulphate and concentrated. The crude oily residue was purified by column chromatography using hexane-ethyl acetate (10:2) to afford 0.4 g of the required product. Percentage purity: 36.3%, (M+1)=567.2. 1H NMR (DMSO-d6): δ 1.35 (3H, m), 1.38 (9H, s), 1.65 (2H, m), 2.71 (2H, m), 2.95 (4H, m), 3.75 (2H, m), 6.80 (1H, t), 6.95 (1H, d), 7.32 (4H, d), 7.68 (1H, m), 7.85 (4H, d).

後処理

  1. temperaturewas maintained below 5° C. during the addition
  2. stirringThe mixture was stirred overnight at RT
  3. concentrationThe solvent was concentrated under reduced pressure
  4. dissolutionthe residue was dissolved in a mixture of water (150 ml) and ethyl acetate (150 ml)
  5. customthe phases were separated
  6. extractionThe aqueous phase was extracted with ethyl acetate
  7. washThe combined organic phase was washed with 10% solution of potassium hydrogen sulphate
  8. dry with materialand saturated brine solution, and dried over sodium sulphate
  9. concentrationconcentrated
  10. customThe crude oily residue was purified by column chromatography

出典と根拠

ORDレコード
ord-eaab48293a2748bdbd0b4271ee4fdea5
出典データセット
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08722930B2

反応ノート

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