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3-Hydroxy-2,2-dimethylpropionic acid → 3-hydroxy-2,2-dimethyl-N-(4-(4-(2-methyl-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(methylthio)tetrahydro-2H-pyran-2-yl)benzyl)phenyl)butyl)propanamide

HRID 1499297
ノート
印刷プレビュー

反応式

HRID 1499297 の反応式
C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@H:9]([O:15]C(=O)C)[C@@H:8]([S:19][CH3:20])[O:7][C@H:6]1[C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][CH2:37][CH2:38][NH2:39])=[CH:31][CH:30]=2)[CH:22]=1)(=O)C.[OH:40][CH2:41][C:42]([CH3:47])([CH3:46])[C:43]([OH:45])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[OH:40][CH2:41][C:42]([CH3:47])([CH3:46])[C:43]([NH:39][CH2:38][CH2:37][CH2:36][CH2:35][C:32]1[CH:31]=[CH:30][C:29]([CH2:28][C:23]2[CH:22]=[C:21]([C@H:6]3[C@H:5]([OH:4])[C@@H:10]([OH:11])[C@H:9]([OH:15])[C@@H:8]([S:19][CH3:20])[O:7]3)[CH:26]=[CH:25][C:24]=2[CH3:27])=[CH:34][CH:33]=1)=[O:45]
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 785483-Hydroxy-2,2-dimethylpropionic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 90177035(2S,3S,4R,5S,6R)-2-(3-(4-(4-aminobutyl)benzyl)-4-methylphenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triyl triacetate

生成物 1

HCID 90183110
3-hydroxy-2,2-dimethyl-N-(4-(4-(2-methyl-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(methylthio)tetrahydro-2H-pyran-2-yl)benzyl)phenyl)butyl)propanamide
収率 41.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of (2S,3S,4R,5S,6R)-2-(3-(4-(4-aminobutyl)benzyl)-4-methylphenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triyl triacetate (19, 55 mg, 0.10 mmol), 3-hydroxy-2,2-dimethylpropanoic acid (18 mg, 0.15 mmol), HATU (57 mg, 0.15 mmol), and DIPEA (52 μL, 0.30 mmol) were combined in DMF (1 mL) and stirred for 4 hours at room temperature. The reaction quenched with saturated aqueous NaHCO3 and extracted twice with EtOAc. The combined organic layers were washed with brine, dried with MgSO4, filtered, and concentrated under vacuum. The residue was dissolved in MeOH and treated with a few drops of NaOMe (25 wt % in MeOH) for 1 hour. The reaction was concentrated under vacuum, and the residue was purified by prep HPLC (C18 30×100 mm column, 5-40% CH3CN/10 mM aqueous ammonium formate, 45 mL/min) to give the title compound 21 as a white solid (22 mg, 41% yield). 1H NMR (400 MHz, MeOH-d4) δ ppm 6.98-7.22 (m, 7 H), 4.39 (d, J=9.6 Hz, 1 H), 4.13 (d, J=9.1 Hz, 1 H), 3.90-3.99 (m, 2 H), 3.49 (s, 2 H), 3.35-3.46 (m, 3 H), 3.19 (t, J=6.9 Hz, 2 H), 2.58 (t, J=7.5 Hz, 2 H), 2.18-2.23 (m, 3 H), 2.14 (s, 3 H), 1.60 (s, 2 H), 1.46-1.57 (m, 2 H), 1.11 (s, 6 H). MS (ES+) [M+H]+=532.

後処理

  1. customThe reaction quenched with saturated aqueous NaHCO3
  2. extractionextracted twice with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. dissolutionThe residue was dissolved in MeOH
  8. additiontreated with a few drops of NaOMe (25 wt % in MeOH) for 1 hour
  9. concentrationThe reaction was concentrated under vacuum
  10. customthe residue was purified by prep HPLC (C18 30×100 mm column, 5-40% CH3CN/10 mM aqueous ammonium formate, 45 mL/min)

出典と根拠

ORDレコード
ord-943fcde0d0c64469a512fde2b0a9e01e
出典データセット
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09200025B2

反応ノート

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