Isonicotinoyl chloride hydrochloride → HCID 91754468, compound

HRID 1484709Notes

Reaction equation

HRID 1484709 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[C:14]([CH3:15])=[CH:13][C:10]([C:11]#[N:12])=[CH:9][C:8]=2[CH3:16])[N:6]=1.Cl.[C:18](Cl)(=[O:25])[C:19]1[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:11]([C:10]1[CH:9]=[C:8]([CH3:16])[C:7]([C:5]2[N:6]=[C:2]([NH:1][C:18](=[O:25])[C:19]3[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=3)[S:3][CH:4]=2)=[C:14]([CH3:15])[CH:13]=1)#[N:12]

Participants

5

Reactant 2

HCID 12262826Isonicotinoyl chloride hydrochlorideHCID 118005909HCID 118005909, compound

Product 1

HCID 91754468HCID 91754468, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(2-Aminothiazol-4-yl)-3,5-dimethylbenzonitrile (84 mg, 0.37 mmol) in DCM (2 mL) was added DMAP (84 mg, 0.74 mmol) followed by isonicotinoyl chloride hydrochloride (85 mg, 0.48 mmol). Then the mixture was stirred at room temperature for one hour. The reaction mixture was concentrated, and the saturated aqueous sodium bicarbonate (30 mL) was added. The aqueous solution was extracted with DCM (3×10 mL). The combined organic layers were dried with anhydrous sodium sulfate. After removal of all the solvent, the residue was purified by silica gel chromatography (hexane/acetone=2:1) to give INH174 (55 mg, 44%) as a white solid; mp 248-250° C. 1H NMR (400 MHz, CD3OD) δ 8.88-8.86 (m, 2H), 7.76-7.74 (m, 2H), 7.38 (s, 2H), 6.91 (s, 1H), 2.16 (s, 6H). 13C NMR (125 MHz, DMSO-d6) δ 150.9, 141.0, 139.7, 139.2, 131.2, 122.2, 119.4, 113.3, 111.0, 20.4. MS (ESI) m/z 335.0 (M+H+). HRMS calculated for C18H14N4SONa (M+Na+), 357.0786. found, 357.0789.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe saturated aqueous sodium bicarbonate (30 mL) was added
  3. extractionThe aqueous solution was extracted with DCM (3×10 mL)
  4. dry with materialThe combined organic layers were dried with anhydrous sodium sulfate
  5. customAfter removal of all the solvent
  6. customthe residue was purified by silica gel chromatography (hexane/acetone=2:1)
  7. customto give INH174 (55 mg, 44%) as a white solid

Sources & evidence

ORD record
ord-41b9634ecada4decad0d564e049b8564
Source dataset
uspto-grants-2016_08
Patent number
US09422275B2

Reaction notes

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