Hydrochloric Acid → 4-[2-(Benzyloxy)-4-fluorophenyl]-5-fluoro-N-(3-{[(2-methoxyethyl)sulfonyl]methyl}phenyl)pyrimidin-2-amine

HRID 514697Notes

Reaction equation

Cl.O1CCOCC1.[CH2:8]([O:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[C:23]1[C:28]([F:29])=[CH:27][N:26]=[C:25](Cl)[N:24]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[CH3:31][O:32][CH2:33][CH2:34][S:35]([CH2:38][C:39]1[CH:40]=[C:41]([CH:43]=[CH:44][CH:45]=1)[NH2:42])(=[O:37])=[O:36]>C(O)CCC.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>[CH2:8]([O:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[C:23]1[C:28]([F:29])=[CH:27][N:26]=[C:25]([NH:42][C:41]2[CH:43]=[CH:44][CH:45]=[C:39]([CH2:38][S:35]([CH2:34][CH2:33][O:32][CH3:31])(=[O:37])=[O:36])[CH:40]=2)[N:24]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

Conditions

Temperature: 140 °C

Procedure

4N solution of hydrogen chloride in dioxane (0.11 mL; 0.45 mmol) was added to a stirred solution of 4-[2-(benzyloxy)-4-fluorophenyl]-2-chloro-5-fluoropyrimidine (150 mg; 0.45 mmol) and 3-{[(2-methoxyethyl)sulfonyl]methyl}aniline (155 mg; 0.68 mmol; UkrOrgSynthesis Ltd.) in 1-butanol (1.0 mL). The batch was stirred at 140° C. for 60 hours. After cooling the batch was diluted with ethyl acetate and sodium bicarbonate solution. The organic phase was filtered using a Whatman filter and concentrated. The residue was purified by preparative HPLC to give the desired product (19 mg; 0.04 mmol).

Workup

temperatureAfter cooling the batch
filtrationThe organic phase was filtered
filtrationfilter
concentrationconcentrated
customThe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-e9569fd204ff4631bbfcc6c6e8445824
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09108926B2

Reaction notes

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