Hydrochloric Acid → HCID 67051942, compound

HRID 1672977Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:11]([C:18]([N:20]2[CH2:23][C:22]([C@@H:25]([NH:27][C:28](=[O:34])[O:29]C(C)(C)C)[CH3:26])([OH:24])[CH2:21]2)=[O:19])=[N:12][N:13]([CH3:17])[C:14](=[O:16])[CH:15]=1.Cl.[CH3:36]O>>[C:28]([OH:29])(=[O:34])[CH3:36].[NH2:27][C@H:25]([C:22]1([OH:24])[CH2:23][N:20]([C:18]([C:11]2[C:10]([NH:9][C:3]3[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=3[F:1])=[CH:15][C:14](=[O:16])[N:13]([CH3:17])[N:12]=2)=[O:19])[CH2:21]1)[CH3:26]

Participants

Reactant 3

HCID 313Hydrochloric Acid

HCID 887Methanol

HCID 59469185HCID 59469185, compound

Product 1

HCID 67051942HCID 67051942, compoundYield 87%

Conditions

Temperature: 60 °C

Procedure

1,1-Dimethylethyl {(1S)-1-[1-({4-[(2-fluoro-4-iodophenyl)amino]-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl}carbonyl)-3-hydroxyazetidin-3-yl]ethyl}carbamate (55 mg, 0.09 mmol), prepared using procedures similar to those described in Example 36, was taken up in methanol (2 mL) and hydrochloric acid (4N in dioxane, 1 mL, 4 mmol) was added and the reaction was stirred at 60° C. for 2 hours. The reaction mixture was concentrated in vacuo and was purified by reverse-phase HPLC followed by lyophilization of the pure fractions to afford 6-({3-[(1S)-1-aminoethyl]-3-hydroxyazetidin-1-yl}carbonyl)-5-[(2-fluoro-4-iodophenyl)amino]-2-methylpyridazin-3(2H)-one acetate as yellow solid (40 mg, 87%). 1H NMR (400 MHz, CDCl3): 10.17 (d, 1H), 7.52-7.46 (m, 2H), 7.09 (t, 1H), 6.13-6.12 (m, 1H), 4.51-4.48 (m, 2H), 4.18-4.03 (m, 2H), 3.73 (d, 3H), 3.35-3.28 (m, 1H), 3.22-2.80 (br, 3H), 1.21-1.19 (m, 3H); MS (EI) for C17H19FIN5O3: 488 (MH+).

Workup

concentrationThe reaction mixture was concentrated in vacuo
customwas purified by reverse-phase HPLC

Sources & evidence

ORD record: ord-b3f683da9c9940f9947e25b204e0e702
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07999006B2

Reaction notes

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