1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 90347083, compound

HRID 590615Notes

Reaction equation

[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(=O)C4C=CC=CC=4)[S:15][CH2:16][C@@H:11]3[CH2:10]2)=[CH:5][CH:4]=1)#[N:2].N12CCCN=C1CCCCC2>CO.C(=O)(O)[O-].[Na+]>[NH2:17][C:14]1[S:15][CH2:16][C@@H:11]2[CH2:10][C@H:9]([C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=3)[O:27][CH2:26][C@:12]2([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=2[F:35])[N:13]=1

Participants

Conditions

Temperature: 80 °C

Procedure

N-[(4aR,6R,8aS)-6-(4-Cyanophenyl)-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C26) (37 mg, 76 μmol, 1 equiv.) was dissolved in methanol (1.9 mL) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.01 mL, 0.06 mmol, 0.8 equiv) was added. The reaction was stirred at 80° C. for 16 hours. The reaction mixture was diluted with 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 50% ethyl acetate in heptane) afforded the product as a white solid. Yield: 27 mg, 91%. LCMS m/z 386.2 [M+H]. 1H NMR (400 MHz, CDCl3) δ 7.64-7.67 (m, 2H), 7.53-7.55 (m, 2H), 7.4 (td, J=9.0, 6.7 Hz, 1H), 6.82-6.95 (m, 2H), 4.73 (dd, J=11.4, 2.2 Hz, 1H), 4.25 (dd, J=11.4, 2.2 Hz, 1H), 4.00 (d, J=11.5 Hz, 1H), 3.11-3.17 (m, 1H), 3.04 (dd, J=12.5, 4.1 Hz, 1H), 2.66 (dd, J=12.5, 2.9 Hz, 1H), 1.95-2.05 (m, 1H), 1.78-1.83 (m, 1H).

Workup

extractionextracted with ethyl acetate (3×20 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-4f17d36d76b94f8290bf06a6350d8724
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09233981B1

Reaction notes

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