Hydrochloric Acid → HCID 67051942, compound

HRID 1717634Notes

Reaction equation

CC([N:5]([C@H:9]([C:11]1([OH:34])[CH2:14][N:13]([C:15]([C:17]2[C:22]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([I:30])=[CH:26][C:25]=3[F:31])=[CH:21][C:20](=[O:32])[N:19]([CH3:33])[N:18]=2)=[O:16])[CH2:12]1)[CH3:10])C(=O)[O-])(C)C.Cl.C[OH:37]>>[C:20]([OH:32])(=[O:37])[CH3:21].[NH2:5][C@H:9]([C:11]1([OH:34])[CH2:14][N:13]([C:15]([C:17]2[C:22]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([I:30])=[CH:26][C:25]=3[F:31])=[CH:21][C:20](=[O:32])[N:19]([CH3:33])[N:18]=2)=[O:16])[CH2:12]1)[CH3:10]

Participants

Reactant 3

HCID 313Hydrochloric Acid

HCID 887Methanol

HCID 86631235HCID 86631235, 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-2490ef80d5d94f588faee9178dde530d
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07803839B2

Reaction notes

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