Hydrochloric Acid → N-(5-(amino(2-chlorophenyl)methyl)-4-methylthiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

HRID 2043239Notes

Reaction equation

HRID 2043239 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[S:17][C:18]([CH:22]([C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=5[Cl:36])[NH:23][S@@](C(C)(C)C)=O)=[C:19]([CH3:21])[N:20]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.Cl.O1CCOCC1>CO>[NH2:23][CH:22]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[Cl:36])[C:18]1[S:17][C:16]([NH:15][C:13]([C:10]2([C:8]3[CH:7]=[CH:6][C:5]4[O:1][CH2:2][O:3][C:4]=4[CH:9]=3)[CH2:12][CH2:11]2)=[O:14])=[N:20][C:19]=1[CH3:21]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86621214HCID 86621214, compound

Product 1

HCID 76672719N-(5-(amino(2-chlorophenyl)methyl)-4-methylthiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-((2-chlorophenyl)((R)-1,1-dimethylethylsulfinamido)methyl)-4-methylthiazol-2-yl)cyclopropanecarboxamide (Isomer A), (1.47 g, 2.69 mmol) in MeOH (13 mL) was added 4 M HCl in dioxane (4 mL, 16 mmol). The reaction mixture was stirred at room temperature for 3 h and then concentrated. The crude product was dissolved in CH2Cl2 and washed with saturated aqueous NaHCO3 solution (×2) and brine, then dried over MgSO4 and concentrated. The crude product was adsorbed onto silica gel and purified by column chromatography (70-100% EtOAc/hexanes) to provide N-(5-(amino(2-chlorophenyl)methyl)-4-methylthiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (Isomer A), as an orange solid (540 mg, 45%). 1H NMR (400 MHz, DMSO-d6) δ 7.80 (d, J=7.9 Hz, 1H), 7.40-7.36 (m, 2H), 7.27 (m, 1H), 6.94 (s, 1H), 6.85 (m, 2H), 6.00 (s, 2H), 5.56 (s, 1H), 2.19 (s, 3H), 1.40 (m, 2H), 1.10 (m, 2H); HPLC ret. time 2.65 min, 10-99% CH3CN, 5 min run; ESI-MS 442.5 m/z (MH+).

Workup

  1. concentrationconcentrated
  2. dissolutionThe crude product was dissolved in CH2Cl2
  3. washwashed with saturated aqueous NaHCO3 solution (×2) and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. custompurified by column chromatography (70-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-74306119632d4a7c92c0d93a22de5b51
Source dataset
uspto-grants-2013_11
Patent number
US08586615B2

Reaction notes

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