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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
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HRID 877745 반응식
[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]
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참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 887Methanol용매
HCID 8028
Tetrahydrofuran
용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-eb0a972e77bf47dcac7d2685a08e766d
출처 데이터셋
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08987268B2

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