2-Amino-4-methylthiazole → 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-N-(4-methyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

HRID 1990001ノート

反応式

HRID 1990001 の反応式
[N:1]1([C:5]([C:7]2[N:8]=[CH:9][C:10]([O:13][C:14]3[CH:15]=[C:16]([CH:20]=[C:21]([O:23][C@H:24]4[CH2:28][CH2:27][O:26][CH2:25]4)[CH:22]=3)[C:17]([OH:19])=O)=[N:11][CH:12]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:53][C:54]1[S:55][CH:56]=[C:57]([CH3:59])[N:58]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[N:1]1([C:5]([C:7]2[N:8]=[CH:9][C:10]([O:13][C:14]3[CH:15]=[C:16]([CH:20]=[C:21]([O:23][C@H:24]4[CH2:28][CH2:27][O:26][CH2:25]4)[CH:22]=3)[C:17]([NH:53][C:54]3[S:55][CH:56]=[C:57]([CH3:59])[N:58]=3)=[O:19])=[N:11][CH:12]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1

参加物

6

反応物 4

HCID 741432-Amino-4-methylthiazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 591271123-{[5-(Azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(3S)-tetrahydrofuran-3-yloxy]benzoic acid

生成物 1

HCID 160399703-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-N-(4-methyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide収率 28%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

3-{[5-(Azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(3S)-tetrahydrofuran-3-yloxy]benzoic acid (200 mg, 0.52 mmol), HATU (475 mg, 1.25 mmol) and 2-amino-4-methylthiazole (119 mg, 1.04 mmol) were suspended in DMF (2 mL). DIPEA (0.220 mL, 1.26 mmol) was then added and the reaction mixture stirred at RT for 16 hours. The DMF was removed in vacuo and water (15 mL) added. The mixture was extracted with ethyl acetate (3×20 mL) and the extracts combined, washed with water (15 mL), 1N hydrochloric acid (10 mL), water (10 mL), a saturated aqueous solution of sodium bicarbonate (10 mL), brine (10 mL), dried (MgSO4), filtered, and evaporated in vacuo. The residue was chromatographed on silica, eluting with a gradient of 60-100% ethyl acetate in isohexane, to give the desired compound (70 mg).

後処理

  1. customThe DMF was removed in vacuo and water (15 mL)
  2. additionadded
  3. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  4. washwashed with water (15 mL), 1N hydrochloric acid (10 mL), water (10 mL)
  5. dry with materiala saturated aqueous solution of sodium bicarbonate (10 mL), brine (10 mL), dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was chromatographed on silica
  9. washeluting with a gradient of 60-100% ethyl acetate in isohexane

出典と根拠

ORDレコード
ord-1f059f51d387420b935ca69171c10f29
出典データセット
uspto-grants-2010_01
特許番号
US07642263B2

反応ノート

読み込み中…