Hydrochloric Acid → HCID 178505096, compound

HRID 705390Notes

Reaction equation

HRID 705390 reaction equation
[CH:1]1([C:4]2[C:5]([N:25]([S:33]([CH3:36])(=[O:35])=[O:34])[CH2:26][CH2:27][CH2:28]/[C:29](=[N:31]/[OH:32])/[NH2:30])=[CH:6][C:7]3[O:11][C:10]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)=[C:9]([C:19]4[NH:20][CH:21]=[CH:22][N:23]=4)[C:8]=3[CH:24]=2)[CH2:3][CH2:2]1.[C:37](N1C=CN=C1)(N1C=CN=C1)=[S:38].N12CCCN=C1CCCCC2.Cl>C(#N)C.C(OCC)(=O)C.O>[CH:1]1([C:4]2[C:5]([N:25]([CH2:26][CH2:27][CH2:28][C:29]3[NH:30][C:37](=[S:38])[O:32][N:31]=3)[S:33]([CH3:36])(=[O:35])=[O:34])=[CH:6][C:7]3[O:11][C:10]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)=[C:9]([C:19]4[NH:20][CH:21]=[CH:22][N:23]=4)[C:8]=3[CH:24]=2)[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 802641,1'-ThiocarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 89955243HCID 89955243, compound

Product 1

HCID 178505096HCID 178505096, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a 5-mL round bottom flask, a solution of Example 176 (25 mg, 0.049 mmol), 1,1′-thiocarbonyldiimidazole (13.75 mg, 0.073 mmol), and 1,8-diazabicyclo[5.4.0]undec-7-ene (30.1 μL, 0.195 mmol) in anhydrous acetonitrile (490 μL) was stirred under nitrogen at 25° C. for 2 hours. The reaction was diluted with ethyl acetate (50 mL) and H2O (10 mL), and the pH was adjusted to ˜3 with 1 N aqueous HCl. The layers were separated, and the organic phase was washed with brine (10 mL), dried over anhydrous MgSO4, filtered, and concentrated by rotary evaporation. The crude material was purified by SiO2 flash chromatography (Alltech Extract-Clean™ column, 10 g bed) eluting with a step gradient of 5% to 7.5% methanol/CH2Cl2 to afford the title compound as a yellow solid (22 mg, 0.039 mmol, 80%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.50-0.62 (m, 1H), 0.81-0.91 (m, 1H), 0.94-1.04 (m, 2H), 1.73-1.89 (m, 2H), 2.34-2.42 (m, 1H), 2.56-2.66 (m, 2H), 3.17 (s, 3H), 3.66-3.85 (m, 2H), 7.10 (s, 1H), 7.35 (t, J=8.89 Hz, 2H), 7.40 (s, 2H), 7.90 (s, 1H), 7.95 (dd, J=8.08, 5.80 Hz, 2H); MS (ESI+) m/z 554 (M+H)+, 1107 (2M+H)+; MS (ESI−) m/z 552 (M−H)−, 1105 (2M−H)−.

Workup

  1. customThe layers were separated
  2. washthe organic phase was washed with brine (10 mL)
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customThe crude material was purified by SiO2 flash chromatography (Alltech Extract-Clean™ column, 10 g bed)
  7. washeluting with a step gradient of 5% to 7.5% methanol/CH2Cl2

Sources & evidence

ORD record
ord-8b88126991364076a1a785eafc40b8fb
Source dataset
uspto-grants-2015_11
Patent number
US09173887B2

Reaction notes

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