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

HRID 877745Notes

Reaction equation

HRID 877745 reaction equation
[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]

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-eb0a972e77bf47dcac7d2685a08e766d
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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