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Diisopropylethylamine → Tert-butyl 3-(3-{[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]carbamoyl}-4-methyl-5-[methyl(oxan-4-yl)amino]phenyl)azetidine-1-carboxylate

HRID 2208816
ノート
印刷プレビュー

反応式

HRID 2208816 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([C:12]2[CH:13]=[C:14]([N:22]([CH3:29])[CH:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[C:15]([CH3:21])=[C:16]([CH:20]=2)[C:17]([OH:19])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:63][CH2:64][C:65]1[C:66](=[O:73])[NH:67][C:68]([CH3:72])=[CH:69][C:70]=1[CH3:71]>CN(C=O)C>[CH3:71][C:70]1[CH:69]=[C:68]([CH3:72])[NH:67][C:66](=[O:73])[C:65]=1[CH2:64][NH:63][C:17]([C:16]1[CH:20]=[C:12]([CH:10]2[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:11]2)[CH:13]=[C:14]([N:22]([CH3:29])[CH:23]2[CH2:24][CH2:25][O:26][CH2:27][CH2:28]2)[C:15]=1[CH3:21])=[O:19]
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 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 708738425-{1-[(Tert-butoxy)carbonyl]azetidin-3-yl}-2-methyl-3-[methyl(oxan-4-yl)amino]benzoic acid

生成物 1

HCID 70913254
Tert-butyl 3-(3-{[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]carbamoyl}-4-methyl-5-[methyl(oxan-4-yl)amino]phenyl)azetidine-1-carboxylate
収率 68.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a stirred solution of 5-{1-[(tert-butoxy)carbonyl]azetidin-3-yl}-2-methyl-3-[methyl(oxan-4-yl)amino]benzoic acid (47 mg, 0.12 mmol) in DMF (2 ml) were added DIPEA (40 μl, 0.23 mmol) and HATU (53 mg, 0.14 mmol) at 0° C. The reaction was stirred at 0° C. for 5 min after which time 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 22 mg, 0.13 mmol) was added and the reaction was warmed room temperature for 16 h. The reaction mixture was then poured onto distilled water (50 ml) and the aqueous phase was extracted with DCM (3×50 ml), washed with brine (50 ml) dried (Na2SO4), filtered and evaporated to give an oil. The product was then purified using a 5 g silica Isolute column eluting with 0% to 5% MeOH in DCM and evaporated to afford the title compound as a colourless oil (44 mg, 67%). LC-MS 96%, m/z=539.4, 1H NMR (500 MHz, Chloroform-d) δ 11.68 (s, 1H), 6.95 (t, J=5.8 Hz, 1H), 6.92 (d, J=4.2 Hz, 2H), 5.88 (s, 1H), 4.47 (d, J=5.8 Hz, 2H), 4.20 (t, J=8.7 Hz, 2H), 3.90 (d, J=11.2 Hz, 2H), 3.86-3.73 (m, 2H), 3.62-3.50 (m, 1H), 3.26 (t, J=10.8 Hz, 2H), 2.89 (ddd, J=14.6, 10.8, 3.7 Hz, 1H), 2.55 (s, 3H), 2.33 (s, 3H), 2.20 (s, 3H), 2.14 (s, 3H), 1.75-1.47 (m, 4H), 1.39 (d, J=5.7 Hz, 9H).

後処理

  1. additionwas added
  2. additionThe reaction mixture was then poured
  3. distillationonto distilled water (50 ml)
  4. extractionthe aqueous phase was extracted with DCM (3×50 ml)
  5. washwashed with brine (50 ml)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customto give an oil
  10. customThe product was then purified
  11. washeluting with 0% to 5% MeOH in DCM
  12. customevaporated

出典と根拠

ORDレコード
ord-0e1ac0070c0545e5a82de07fd13ac6da
出典データセット
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09376422B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート