Diisopropylethylamine → (S)-Methyl 6-(((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)nicotinate

HRID 2370862ノート

反応式

HRID 2370862 の反応式
Cl.[F:2][C:3]1[CH:4]=[C:5]([C@@H:14]([C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][N:17]=2)[NH2:15])[CH:6]=[CH:7][C:8]=1[O:9][C:10]([F:13])([F:12])[F:11].[CH3:23][O:24][C:25]([C:27]1[CH:28]=[CH:29][C:30]([C:33](O)=[O:34])=[N:31][CH:32]=1)=[O:26].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.O>[F:2][C:3]1[CH:4]=[C:5]([C@H:14]([NH:15][C:33]([C:30]2[CH:29]=[CH:28][C:27]([C:25]([O:24][CH3:23])=[O:26])=[CH:32][N:31]=2)=[O:34])[C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][C:10]([F:13])([F:12])[F:11]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 3149925-(Methoxycarbonyl)pyridine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86687985(S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride2 回

生成物 1

HCID 71144087(S)-Methyl 6-(((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)nicotinate

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of (S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride (17.0 g, 49.9 mmol, Intermediate 6) in DMF (166 mL, Aldrich) was added 5-(methoxycarbonyl)pyridine-2-carboxylic acid (9.94 g, 54.9 mmol, Oakwood Products, Inc.), HATU (20.87 g, 54.9 mmol, Accela ChemBio, Inc.), and DIPEA (18.23 mL, 105 mmol, EMD Biosciences, Inc.). The resulting mixture was then stirred at room temperature for 18 h. Water (400 mL) was then added and the mixture was extracted with EtOAc (2×200 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was then dissolved in MeOH (500 mL) and silica gel was added. The mixture was concentrated and dried in vacuo. The solid mixture was purified by silica gel flash column chromatography using ISCO instrument (solid loading, 0-100% EtOAc/hexane) to give the title compound as a white solid. MS (ESI, positive ion) m/z: 468 (M+H).

後処理

  1. extractionthe mixture was extracted with EtOAc (2×200 mL)
  2. dry with materialThe combined organic extracts were dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was then dissolved in MeOH (500 mL)
  5. additionsilica gel was added
  6. concentrationThe mixture was concentrated
  7. customdried in vacuo
  8. customThe solid mixture was purified by silica gel flash column chromatography

出典と根拠

ORDレコード
ord-839135cafc3b41cd90196ffe4108b93e
出典データセット
uspto-grants-2014_04
特許番号
US08710043B2

反応ノート

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