Sodium Hydroxide → 2-(3-Carbamoyl-2-(3-chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-5-carboxamido)-2-methylpropanoic acid

HRID 920733Notes

Reaction equation

HRID 920733 reaction equation
[C:1]([C:4]1[C:5]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[C:26]([Cl:31])[CH:25]=2)=[N:6][N:7]2[CH2:12][CH2:11][N:10]([C:13]([NH:15][C:16]([CH3:23])([CH3:22])[C:17]([O:19]CC)=[O:18])=[O:14])[CH2:9][C:8]=12)(=[O:3])[NH2:2].[OH-].[Na+]>C(O)C.C1COCC1.O>[C:1]([C:4]1[C:5]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[C:26]([Cl:31])[CH:25]=2)=[N:6][N:7]2[CH2:12][CH2:11][N:10]([C:13]([NH:15][C:16]([CH3:23])([CH3:22])[C:17]([OH:19])=[O:18])=[O:14])[CH2:9][C:8]=12)(=[O:3])[NH2:2]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 118060405Ethyl 2-(3-carbamoyl-2-(3-chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-5-carboxamido)-2-methylpropanoate

Product 1

HCID 1180618892-(3-Carbamoyl-2-(3-chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-5-carboxamido)-2-methylpropanoic acidYield 85.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Intermediate 213A (500 mg, 1.106 mmol) in ethanol (20 mL) and THF (20 mL) was added a solution of NaOH (89 mg, 2.213 mmol) in water (10 mL) and the reaction mixture was stirred at RT for 8 h. The reaction mixture was concentrated to dryness under reduced pressure. The crude product was dissolved in water and the pH of solution was adjusted to 4 using a 1.5N aqueous solution of HCl which was then stirred for 10 min. The precipitate was filtered, dried and triturated with diethyl ether to afford Intermediate 213B as pale brown solid (400 mg, 85%). MS(ES): m/z=424 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 11.99 (s, 1H), 7.89-7.84 (m, 1H), 7.73-7.67 (m, 1H), 7.50-7.44 (m, 1H), 7.35 (s, 1H), 7.20 (br. s., 1H), 6.93 (s, 1H), 4.74 (s, 2H), 4.16-4.10 (m, 2H), 3.85 (d, J=5.5 Hz, 2H), 1.38 (s, 6H).

Workup

  1. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
  2. dissolutionThe crude product was dissolved in water
  3. stirringwas then stirred for 10 min
  4. filtrationThe precipitate was filtered
  5. customdried
  6. customtriturated with diethyl ether

Sources & evidence

ORD record
ord-a6bf934661694de685a4db420dabc189
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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