Hydrochloric Acid → 2-[4-(2-Chloro-phenylamino)-6-oxo-6h-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((r)-2,3-dihydroxy-propyl)-1h-pyrazol-3-yl]-amide

HRID 2381546Notes

Reaction equation

HRID 2381546 reaction equation
CC1(C)[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:35])[CH:15]([N:20]3[C:25](=[O:26])[CH:24]=[C:23]([NH:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[Cl:34])[CH:22]=[N:21]3)[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]2)[CH2:4][O:3]1.Cl>O1CCCC1>[OH:6][C@@H:5]([CH2:4][OH:3])[CH2:7][N:8]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:35])[CH:15]([N:20]2[C:25](=[O:26])[CH:24]=[C:23]([NH:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[Cl:34])[CH:22]=[N:21]2)[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 668931232-[4-(2-chloro-phenylamino)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide

Product 1

HCID 579192422-[4-(2-Chloro-phenylamino)-6-oxo-6h-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((r)-2,3-dihydroxy-propyl)-1h-pyrazol-3-yl]-amideYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2-[4-(2-chloro-phenylamino)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (41.2 mg, 0.08 mmol) in tetrahydrofuran (2 mL) was treated with a 1 M aqueous hydrochloric acid solution (2 mL), and the reaction stirred at 25° C. overnight. At this point, the reaction was dried under nitrogen and suspended in ethyl acetate (20 mL), then washed with a 1:1 aqueous sodium bicarbonate/water solution (20 mL total) and a saturated aqueous sodium chloride solution (10 mL). The organics were dried over sodium sulfate, concentrated in vacuo, and dried from methylene chloride, ethanol, and diethyl ether, and in a vacuum oven at 50° C. for 3 h to afford 2-[4-(2-chloro-phenylamino)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide as a light yellow solid (29.6 mg, 78%); ES+-HRMS m/e calcd for C22H27N6O4Cl [M+H+] 475.1855 found 475.1855. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.86 (d, J=6.6 Hz, 3H), 0.88 (d, J=6.6 Hz, 3H), 1.44 (br. s., 1H), 1.62-1.81 (m, 1H), 2.00-2.22 (m, 1H), 3.20-3.32 (m, 2H), 3.70-3.92 (m, 2H), 4.08 (dd, J=13.4, 3.8 Hz, 1H), 4.71 (t, J=5.6 Hz, 1H), 4.94 (dd, J=5.1, 1.8 Hz, 1H), 5.49 (dd, J=11.0, 4.1 Hz, 1H), 5.54 (d, J=2.7 Hz, 1H), 6.35 (d, J=2.1 Hz, 1H), 7.28 (td, J=7.8, 1.2 Hz, 1H), 7.40 (td, J=7.8, 1.2 Hz, 1H), 7.47 (dd, J=7.8, 1.2 Hz, 1H), 7.52 (d, J=2.1 Hz, 1H), 7.60 (dd, J=7.8, 1.2 Hz, 1H), 7.86 (d, J=2.7 Hz, 1H), 8.94 (s, 1H), 10.65 (s, 1H).

Workup

  1. customAt this point, the reaction was dried under nitrogen
  2. washwashed with a 1:1 aqueous sodium bicarbonate/water solution (20 mL total)
  3. dry with materialThe organics were dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dry with materialdried from methylene chloride, ethanol, and diethyl ether

Sources & evidence

ORD record
ord-b8216088208a49d7a309d9b44b54e098
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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