Pyridine → N-[(4aR,6R,8aS)-8a-(5-cyano-2-fluorophenyl)-6-cyclopropyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 68435Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([F:31])=[C:6]([C@@:8]2([NH:19][C:20]([NH:22][C:23](=[O:30])[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[S:21])[C@H:13]([CH2:14]O)[CH2:12][C@H:11]([CH:16]3[CH2:18][CH2:17]3)[O:10][CH2:9]2)[CH:7]=1.[N:32]1C=CC=C[CH:33]=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>ClCCl>[C:33]([C:2]1[CH:3]=[CH:4][C:5]([F:31])=[C:6]([C@:8]23[CH2:9][O:10][C@@H:11]([CH:16]4[CH2:18][CH2:17]4)[CH2:12][C@H:13]2[CH2:14][S:21][C:20]([NH:22][C:23](=[O:30])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[N:19]3)[CH:7]=1)#[N:32]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of N-{[(3S,4R,6R)-3-(5-bromo-2-fluorophenyl)-6-cyclopropyl-4-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]carbamothioyl}benzamide (C57) (127 mg, 0.28 mmol) and pyridine (81 μL, 1.01 mmol) in dichloromethane (12 mL) was cooled to −50° C. Trifluoromethanesulfonic anhydride (94 μL, 0.56 mmol) was added drop-wise to the solution and the mixture was gradually warmed to 0° C. over 90 minutes. The reaction mixture was diluted with dichloromethane (20 mL), washed with water (2×30 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane) afforded the product as a solid. Yield: 83 mg, 68%. LCMS m/z 436.2 [M+H+].

Workup

washwashed with water (2×30 mL)
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customPurification via silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane)

Sources & evidence

ORD record: ord-bec2dca1ecfb44ba8ed9b389468d64ec
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822456B2

Reaction notes

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