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Sodium Hydroxide → (R)-4-((1-(tert-butoxycarbonyl)-3,3-dimethylpiperidin-4-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylic acid

HRID 877745
ノート
印刷プレビュー

反応式

HRID 877745 の反応式
[OH-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C@@H:13]([NH:16][C:17]2[C:18]3[N:19]([CH:26]=[C:27]([C:29]([O:31]CC)=[O:30])[CH:28]=3)[N:20]=[CH:21][C:22]=2[C:23](=[O:25])[NH2:24])[C:12]([CH3:35])([CH3:34])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>CO.O1CCCC1>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C@@H:13]([NH:16][C:17]2[C:18]3[N:19]([CH:26]=[C:27]([C:29]([OH:31])=[O:30])[CH:28]=3)[N:20]=[CH:21][C:22]=2[C:23](=[O:25])[NH2:24])[C:12]([CH3:35])([CH3:34])[CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]
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 14798Sodium HydroxideHCID 68350368(R)-ethyl 4-((1-(tert-butoxycarbonyl)-3,3-dimethylpiperidin-4-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylate

生成物 1

HCID 68291940(R)-4-((1-(tert-butoxycarbonyl)-3,3-dimethylpiperidin-4-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylic acid収率 101.5%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒
HCID 8028
Tetrahydrofuran
溶媒

実験手順

A 2 M aqueous solution of sodium hydroxide (6 mL, 12.00 mmol) was added to a solution of (R)-ethyl 4-((1-(tert-butoxycarbonyl)-3,3-dimethylpiperidin-4-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylate (1.187 g, 2.58 mmol) in methanol (11 mL) and tetrahydrofuran (11 mL) at room temperature. The resulting mixture was heated at reflux for 40 min and cooled to room temperature. The organic solvents were evaporated in vacuo. The residue was neutralized to pH 5 with 1 N HCl. The resulting precipitate was collected by filtration to give (R)-4-((1-(tert-butoxycarbonyl)-3,3-dimethylpiperidin-4-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylic acid as brown solid (1.13 g, 97% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.57 (br. s., 1H), 11.16 (d, J=8.8 Hz, 1H), 8.31 (s, 1H), 8.05 (d, J=1.3 Hz, 1H), 7.23 (s, 1H), 4.12-4.00 (m, 1H), 3.87 (br. s., 1H), 3.56 (d, J=12.8 Hz, 1H), 3.01 (br. s., 2H), 1.91 (dd, J=13.5, 3.2 Hz, 1H), 1.56 (d, J=8.1 Hz, 1H), 1.41 (s, 9H), 0.98 (s, 3H), 0.92 (s, 3H); MS (ES+) m/z: 432.2 (M+H); LC retention time: 3.795 min (analytical HPLC Method H).

後処理

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 40 min
  3. customThe organic solvents were evaporated in vacuo
  4. filtrationThe resulting precipitate was collected by filtration

出典と根拠

ORDレコード
ord-eb0a972e77bf47dcac7d2685a08e766d
出典データセット
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08987268B2

反応ノート

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