Trifluoroacetic acid → HCID 90344976, compound

HRID 590614Notes

Reaction equation

HRID 590614 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:27][CH2:26][C@:12]3([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=4[F:35])[N:13]=[C:14]([NH:17][C:18](=[O:25])[C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[S:15][CH2:16][C@@H:11]3[CH:10]=2)=[CH:5][CH:4]=1)#[N:2].C([SiH](CC)CC)C.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCCl>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[O:27][CH2:26][C@:12]3([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=4[F:35])[N:13]=[C:14]([NH:17][C:18](=[O:25])[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[S:15][CH2:16][C@@H:11]3[CH2:10]2)=[CH:5][CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 516892Sodium BicarbonateHCID 90347084HCID 90347084, compound

Product 1

HCID 90344976HCID 90344976, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

N-[(4aR,8aS)-6-(4-Cyanophenyl)-8a-(2,4-difluorophenyl)-4,4a,8,8a-tetrahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C25) (64 mg, 0.13 mmol, 1 equiv) was dissolved in 1,2-dichloroethane (2.0 mL) and cooled to 0° C. Triethylsilane (0.32 mL, 2.0 mmol, 15 equiv) and trifluoroacetic acid (0.5 mL) were added and reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was neutralized by addition of a saturated solution of sodium bicarbonate (10 mL) and extracted with ethyl acetate (3×20 mL). The organics were combined, dried over sodium sulfate, filtered and concentrated in vacuo. Chromatography on silica gel (Gradient: 0% to 30% ethyl acetate in heptane) afforded the product as a white solid. Yield: 37 mg, 58%. LCMS m/z 490.3 [M+H+]. 1H NMR (400 mhz, CDCL3) δ 8.24 (d, J=7.0 Hz, 2H), 7.63-7.66 (m, 2H), 7.41-7.56 (m, 5H), 6.90-7.01 (m, 2H), 4.78 (dd, J=11.5, 2.3 Hz, 1H), 4.33 (dd, J=12.3, 1.6 Hz, 1H), 3.99 (d, J=12.3 Hz, 1H), 3.32-3.36 (m, 1H), 3.07 (dd, J=12.9, 4.1 Hz, 1H), 2.68 (dd, J=12.9, 2.7 Hz, 1H), 2.12-2.22 (m, 1H), 1.91-1.96 (m, 1H).

Workup

  1. customreaction mixture
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ef6577eb5ecc41c7adaca28b3cc0d354
Source dataset
uspto-grants-2016_01
Patent number
US09233981B1

Reaction notes

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