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1,4-Dioxane → (5S)-5-amino-1-[6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]piperidin-2-one

HRID 57905
ノート
印刷プレビュー

反応式

HRID 57905 の反応式
[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[N:13]=[CH:12][C:11]3[CH:14]=[N:15][N:16]([C:17]4[N:22]=[C:21]([N:23]5[C:28](=[O:29])[CH2:27][CH2:26][C@H:25]([NH:30]C(=O)OC(C)(C)C)[CH2:24]5)[CH:20]=[CH:19][CH:18]=4)[C:10]=3[CH:9]=2)[CH:5]=[N:4][CH:3]=1.O1CCOCC1>Cl.O>[NH2:30][C@@H:25]1[CH2:24][N:23]([C:21]2[CH:20]=[CH:19][CH:18]=[C:17]([N:16]3[C:10]4[CH:9]=[C:8]([C:6]5[CH:5]=[N:4][CH:3]=[C:2]([CH3:1])[N:7]=5)[N:13]=[CH:12][C:11]=4[CH:14]=[N:15]3)[N:22]=2)[C:28](=[O:29])[CH2:27][CH2:26]1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 2

HCID 312751,4-Dioxane2 回HCID 86707097tert-butyl N-[(3S)-1-[6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-6-oxo-3-piperidyl]carbamate

生成物 1

HCID 72715703(5S)-5-amino-1-[6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]piperidin-2-one収率 18.3%

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒
HCID 962
Water
溶媒

実験手順

A solution of tert-butyl N-[(3S)-1-[6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-6-oxo-3-piperidyl]carbamate (45 mg, 0.15 mmol) in hydrogen chloride (4 mol/l) in 1,4-dioxane (2.0 ml, 8.0 mmol) and 1,4-dioxane 2.0 mL was stirred at RT 18 h. The reaction was diluted with water then wash with EtOAc. The aqueous layer was basified with 1M NaOH to pH 10 and extracted with EtOAc. The organic layers was dried with sodium sulfate, filtered, and concentrated in vacuum. The crude product was submitted for reverse phase HPLC to give 202 (11 mg) in 18% yield. MS (ESI) m/z: 401.1. 1H NMR (400 MHz, DMSO) δ 9.61 (s, 1H), 9.47 (s, 1H), 9.35 (s, 1H), 8.73 (s, 1H), 8.63 (s, 1H), 8.04 (t, J=8.1 Hz, 1H), 7.83 (d, J=7.9 Hz, 1H), 7.76 (d, J=8.1 Hz, 1H), 4.24 (dd, J=12.2, 3.8 Hz, 1H), 3.94 (dd, J=12.3, 6.3 Hz, 1H), 3.49 (s, 1H), 2.75 (dd, J=12.2, 5.3 Hz, 1H), 2.69 (s, 3H), 2.63-2.55 (m, 1H), 2.10 (dd, J=13.0, 4.3 Hz, 1H), 1.85-1.72 (m, 1H).

後処理

  1. washthen wash with EtOAc
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layers was dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum

出典と根拠

ORDレコード
ord-97f20c65ba5f479f8eb4a994f7a49022
出典データセット
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09434725B2

反応ノート

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