Ethanol → HCID 135936707, compound

HRID 421487Notes

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]([CH:68]1[CH2:72][CH2:71][CH2:70][CH2:69]1)[CH2:58][NH:59][CH2:60][C:61]1[CH:66]=[CH:65][C:64]([F:67])=[CH:63][CH:62]=1)C.[O-]CC.[Na+].C(O)C>CN(C)C=O>[CH:68]1([CH:57]2[CH2:58][N:59]([CH2:60][C:61]3[CH:66]=[CH:65][C:64]([F:67])=[CH:63][CH:62]=3)[C:19](=[O:21])[C:18]([C:12]3[NH:11][C:10]4[S:9][CH:8]=[C:7]([CH2:6][NH:5][S:2]([CH3:1])(=[O:3])=[O:4])[C:15]=4[S:14](=[O:16])(=[O:17])[N:13]=3)=[C:56]2[OH:55])[CH2:72][CH2:71][CH2:70][CH2:69]1

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; 0.120 g, 0.340 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.142 g, 0.373 mmol) and 4-methylmorpholine (0.075 mL, 0.682 mmol) were added sequentially to a solution of rac-2-cyclopentyl-3-(4-fluoro-benzylamino)-propionic acid ethyl ester (0.100 g, 0.341 mmol) in N,N-dimethylformamide (5 mL) at 25° C. The reaction mixture was stirred at 25° C. for 19 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 (12 mL) at 25° C. A 21 wt. % solution of sodium ethoxide in ethanol (0.663 mL, 2.04 mmol) was added and the reaction mixture was heated to 70° C. for 66 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) N-{3-[5-cyclopentyl-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 (0.036 g, 0.062 mmol, 18%) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.07-1.12 (1H, m), 1.16-1.62 (7H, m), 1.76-1.86 (1H, m), 2.28-2.35 (1H, m), 2.95 (3H, s), 3.21 (1H, d, J=14.9 Hz), 3.63 (1H, dd, J1=4.0 Hz, J2=14.0 Hz), 4.24 (2H, d, J=6.3 Hz), 4.34 (1H, d, J=14.6 Hz), 4.85 (1H, d, J=14.2 Hz), 7.15-7.19 (2H, m), 7.25 (1H, s), 7.37-7.40 (2H, m), 7.64 (1H, t, J=6.4 Hz). LC-MS (ESI) calculated for C24H27FN4O6S3 582.11. found 583.1 [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 (12 mL) at 25° C
temperaturethe reaction mixture was heated to 70° C. for 66 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-e815a17dea4948cca64bbb74319f08f3
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08097613B2

Reaction notes

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