2,6-Lutidine → HCID 90253449, compound

HRID 1478710Notes

Reaction equation

HRID 1478710 reaction equation
FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[F:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1[C@:24]12[CH2:33][O:32][C@@H:31]([CH:34]([OH:39])[CH2:35][CH2:36][CH2:37]O)[CH2:30][C@H:29]1[CH2:28][S:27][C:26]([NH:40][C:41](=[O:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[N:25]2.CC1C=CC=C(C)N=1>ClCCl>[F:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1[C@:24]12[CH2:33][O:32][C@@H:31]([CH:34]3[CH2:35][CH2:36][CH2:37][O:39]3)[CH2:30][C@H:29]1[CH2:28][S:27][C:26]([NH:40][C:41](=[O:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[N:25]2

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 67749Trifluoromethanesulfonic anhydrideHCID 90253453HCID 90253453, compound

Product 1

HCID 90253449HCID 90253449, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Trifluoromethanesulfonic anhydride (12.5 μL, 76 μmol) was added drop-wise to a −78° C. solution of N-[(4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(1,4-dihydroxybutyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C12) (18 mg, 38 μmol) and 2,6-dimethylpyridine (17.6 μL, 152 μmol) in dichloromethane (0.65 mL), and the reaction mixture was allowed to gradually warm to 0° C. over 30 minutes. The reaction mixture was partitioned between dichloromethane (10 mL) and water (5 mL), and the organic layer was washed with water (2×5 mL) and with saturated aqueous sodium chloride solution (5 mL), then dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel chromatography (Gradient: 0% to 60% ethyl acetate in heptane) afforded the product as an off-white foam. Yield: 14.7 mg, 32.1 μmol, 84%. LCMS m/z 459.2 [M+H+]. 1H NMR (400 MHz, CDCl3), characteristic peaks: δ 8.23 (br d, J=7.6 Hz, 2H), 7.36-7.55 (m, 4H), 6.84-6.97 (m, 2H), 4.17 (br d, J=12 Hz, 1H), 3.76-3.94 (m, 4H), 3.63-3.70 (m, 1H), 3.11-3.20 (m, 1H), 3.03 (dd, J=12.8, 4.2 Hz, 1H), 2.65 (br d, J=13 Hz, 1H), 1.83-2.06 (m, 4H).

Workup

  1. customThe reaction mixture was partitioned between dichloromethane (10 mL) and water (5 mL)
  2. washthe organic layer was washed with water (2×5 mL) and with saturated aqueous sodium chloride solution (5 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ee11ebf92a594585a179645f23e5a6a6
Source dataset
uspto-grants-2016_08
Patent number
US09403846B2

Reaction notes

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