p-Toluenesulfonic acid → HCID 68992316, compound

HRID 2381527Notes

Reaction equation

HRID 2381527 reaction equation
[CH:1]1([CH2:6][CH:7]([N:24]2[C:29](=[O:30])[CH:28]=[C:27]([O:31][C:32]3[C:37]([F:38])=[CH:36][CH:35]=[CH:34][C:33]=3[F:39])[CH:26]=[N:25]2)[C:8]([NH:10][C:11]2[CH:16]=[N:15][C:14]([C@@H:17]3[CH2:21][O:20]C(C)(C)[O:18]3)=[CH:13][N:12]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO.C(Cl)Cl.C(OCC)(=O)C>[CH:1]1([CH2:6][CH:7]([N:24]2[C:29](=[O:30])[CH:28]=[C:27]([O:31][C:32]3[C:37]([F:38])=[CH:36][CH:35]=[CH:34][C:33]=3[F:39])[CH:26]=[N:25]2)[C:8]([NH:10][C:11]2[CH:16]=[N:15][C:14]([C@@H:17]([OH:18])[CH2:21][OH:20])=[CH:13][N:12]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 68988703HCID 68988703, compound

Product 1

HCID 68992316HCID 68992316, compoundYield 81%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[5-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-propionamide (685 mg, 1.26 mmol) in methanol (12.6 mL, 0.1 M) and methylene chloride (5 mL) was treated with para-toluenesulfonic acid (36 mg, 0.18 mmol). The reaction stirred at 25° C. overnight. At this time, the reaction was diluted with ethyl acetate (100 mL) and washed with a saturated aqueous sodium bicarbonate solution (150 mL), water (150 mL), and a saturated aqueous sodium chloride solution (150 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo to afford 3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[5-((R)-1,2-dihydroxy-ethyl)-pyrazin-2-yl]-propionamide as an off-white solid (0.50 g, 81%); ES+-HRMS m/e calcd for C24H25N5O5F2 [M+H+] 502.1897 found 502.1894. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.04-1.21 (m, 1H), 1.27-1.85 (m, 8H), 1.91-2.08 (m, 1H), 2.22-2.41 (m, 1H), 3.50-3.62 (m, 1H), 3.62-3.73 (m, 1H), 4.62 (q, J=5.1 Hz, 1H), 4.72 (t, J=5.7 Hz, 1H), 5.52-5.64 (m, 2H), 6.07 (d, J=2.5 Hz, 1H), 7.33-7.56 (m, 3H), 8.31 (d, J=2.5 Hz, 1H), 8.45 (s, 1H), 9.13 (s, 1H), 11.25 (br. s., 1H).

Workup

  1. washwashed with a saturated aqueous sodium bicarbonate solution (150 mL), water (150 mL)
  2. dry with materialThe organics were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d50c218497a843f49ce6c0537b7c441f
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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