Ethanol → HCID 136132941, compound

HRID 421491Notes

Reaction equation

[CH3:1][S:2]([NH:5][CH2:6][C:7]1[C:15]2[S:14](=[O:17])(=[O:16])[N:13]=[C:12]([CH2:18][C:19]([OH:21])=O)[NH:11][C:10]=2[S:9][CH:8]=1)(=[O:4])=[O:3].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CN1CCOCC1.C([O:55][C:56](=O)[CH:57]([CH2:60][NH:61][CH2:62][C:63]1[CH:68]=[CH:67][C:66]([F:69])=[CH:65][CH:64]=1)[CH2:58][CH3:59])C.[O-]CC.[Na+].C(O)C>CN(C)C=O>[CH2:58]([CH:57]1[CH2:60][N:61]([CH2:62][C:63]2[CH:64]=[CH:65][C:66]([F:69])=[CH:67][CH:68]=2)[C:19](=[O:21])[C:18]([C:12]2[NH:11][C:10]3[S:9][CH:8]=[C:7]([CH2:6][NH:5][S:2]([CH3:1])(=[O:3])=[O:4])[C:15]=3[S:14](=[O:16])(=[O:17])[N:13]=2)=[C:56]1[OH:55])[CH3:59]

Participants

Conditions

Temperature: 25 °C

Procedure

[7-(Methanesulfonylamino-methyl)-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-acetic acid (prepared as described in Example 2c; 0.113 g, 0.320 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.134 g, 0.352 mmol) and 4-methylmorpholine (0.070 mL, 0.637 mmol) were added sequentially to a solution of rac-2-[(4-fluoro-benzylamino)-methyl]-butyric acid ethyl ester (0.081 g, 0.320 mmol) in N,N-dimethylformamide (4 mL) at 25° C. The reaction mixture was stirred at 25° C. for 18 h, and then was concentrated in vacuo. The residue was partitioned between 1.0 M aqueous hydrochloric acid solution (100 mL) and ethyl acetate (2×100 mL). The organic layers were dried over sodium sulfate and were concentrated in vacuo. The residue was dissolved in ethanol (10 mL) at 25° C. A 21 wt. % solution of sodium ethoxide in ethanol (0.622 mL, 1.92 mmol) was added and the reaction mixture was heated to 70° C. for 18 h. After cooling to 25° C., the reaction mixture was partitioned between 1.0 M aqueous hydrochloric acid solution (100 mL) and ethyl acetate (2×100 mL). The organic layers were dried over sodium sulfate and were concentrated in vacuo. The residue was purified by flash chromatography (Teledyne Isco RediSep column; 50-100% ethyl acetate in hexanes) to afford (after trituration with diethylether) rac-N-{3-[5-ethyl-1-(4-fluoro-benzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydro-pyridin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-7-ylmethyl}-methanesulfonamide (0.061 g, 0.112 mmol, 35%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 0.78 (3H, t, J=7.0 Hz), 1.30-1.38 (1H, m), 1.60-1.66 (1H, m), 2.95 (3H, s), 3.22 (1H, dd, J=4.5 Hz, J2=12.1 Hz), 3.56 (1H, dd, J=4.2 Hz, J2=12.8 Hz), 4.24 (2H, d, J=6.3 Hz), 4.45 (1H, d, J=14.7 Hz), 4.75 (1H, d, J=14.9 Hz), 7.14-7.18 (2H, m), 7.25 (1H, s), 7.36-7.39 (2H, m), 7.64 (1H, t, J=5.0 Hz). LC-MS (ESI) calculated for C21H23FN4O6S3 542.08. found 543.0 [M+H+].

Workup

concentrationwas concentrated in vacuo
customThe residue was partitioned between 1.0 M aqueous hydrochloric acid solution (100 mL) and ethyl acetate (2×100 mL)
dry with materialThe organic layers were dried over sodium sulfate
concentrationwere concentrated in vacuo
dissolutionThe residue was dissolved in ethanol (10 mL) at 25° C
temperaturethe reaction mixture was heated to 70° C. for 18 h
temperatureAfter cooling to 25° C.
customthe reaction mixture was partitioned between 1.0 M aqueous hydrochloric acid solution (100 mL) and ethyl acetate (2×100 mL)
dry with materialThe organic layers were dried over sodium sulfate
concentrationwere concentrated in vacuo
customThe residue was purified by flash chromatography (Teledyne Isco RediSep column; 50-100% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-84a2cd6b5e7940888c88bed05bf7af74
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08097613B2

Reaction notes

Loading…