2-Hydroxyisobutyric acid → Pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 877754ノート

反応式

HRID 877754 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:9](N[C@@H]3CCNC[C@H]3CC)=[C:8]([C:19]([NH2:21])=[O:20])[CH:7]=[N:6][N:5]2[CH:22]=1.OC(C)(C)C(O)=O.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>ClCCl>[N:6]1[N:5]2[CH:22]=[CH:2][CH:3]=[C:4]2[CH:9]=[C:8]([C:19]([NH2:21])=[O:20])[CH:7]=1

参加物

6

反応物 4

HCID 116712-Hydroxyisobutyric acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 682916696-bromo-4-(((3R,4R)-3-ethylpiperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

生成物 1

HCID 68291771Pyrrolo[1,2-b]pyridazine-3-carboxamide収率 70.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 6-bromo-4-(((3R,4R)-3-ethylpiperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (275 mg, 0.75 mmol) and 2-hydroxy-2-methylpropanoic acid (156 mg, 1.501 mmol) in dichloromethane (3.8 ml) were added DIEA (1.3 ml, 7.5 mmol) and HATU (571 mg, 1.501 mmol). The reaction was stirred at room temperature for 14 hrs. The product mixture was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified via medium pressure chromatography (silica gel column, EtOAc/hexanes eluent, 0-100% gradient elution) to yield 6-bromo-4-((3R,4R)-3-ethyl-1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl)amino)pyrrolo-[1,2-b]pyridazine-3-carboxamide (240 mg, 0.531 mmol, 70.7% yield) as a white solid. LCMS (Method K) m/z 454.4 ([M+H]+).

後処理

  1. customThe product mixture was partitioned between ethyl acetate and water
  2. washThe ethyl acetate layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified via medium pressure chromatography (silica gel column, EtOAc/hexanes eluent, 0-100% gradient elution)

出典と根拠

ORDレコード
ord-e3e0591ba9d748b7810b24c9b44bac36
出典データセット
uspto-grants-2015_03
特許番号
US08987268B2

反応ノート

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