Dimethyl Disulfide → 3-(benzyloxy)-N-(4-methylthiazol-2-yl)-5-(methylthio)pyridin-2-amine

HRID 1426091Notes

Reaction equation

HRID 1426091 reaction equation
Cl.[CH2:2]([O:9][C:10]1[C:11]([NH:17][C:18]2[S:19][CH:20]=[C:21]([CH3:23])[N:22]=2)=[N:12][CH:13]=[C:14](Br)[CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Li]C.C([Li])CCC.[CH3:31][S:32]SC.[Cl-].[NH4+]>C1COCC1>[CH2:2]([O:9][C:10]1[C:11]([NH:17][C:18]2[S:19][CH:20]=[C:21]([CH3:23])[N:22]=2)=[N:12][CH:13]=[C:14]([S:32][CH3:31])[CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 5

HCID 12232Dimethyl DisulfideHCID 25517Ammonium ChlorideHCID 160614653-(benzyloxy)-5-bromo-N-(4-methylthiazol-2-yl)pyridin-2-amine hydrochlorideHCID 178418339ButyllithiumHCID 178418348HCID 178418348, compound

Product 1

HCID 592256943-(benzyloxy)-N-(4-methylthiazol-2-yl)-5-(methylthio)pyridin-2-amineYield 74.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

3-(Benzyloxy)-5-bromo-N-(4-methylthiazol-2-yl)pyridin-2-amine (prepared according to Example 1; 0.250 g, 0.664 mmol) was added to THF (30 mL) and cooled to −78° C. MeLi (0.519 mL, 0.831 mmol) was slowly added, and the reaction mixture was stirred for 10 minutes. Butyllithium (0.332 mL, 0.831 mmol) was added, and the reaction mixture was stirred for 15 minutes. 1,2-Dimethyldisulfane (0.438 g, 4.65 mmol) was added, and the reaction mixture was stirred for 15 minutes. Ammonium chloride was added, and the reaction mixture was extracted with CH2Cl2. The organic layer was purified by silica gel (10-20% EtOAc in hexanes) to give 3-(benzyloxy)-N-(4-methylthiazol-2-yl)-5-(methylthio)pyridin-2-amine (0.170 g, 74.5% yield). A portion of this compound was dissolved in dichloromethane, 2M HCl in ether was added, and the mixture was concentrated to give the title compound. 1H NMR (CDCl3) δ 12.30 (bs, 1H), 7.84 (m, 1H), 7.57 (d, 2H), 7.39 (m, 2H), 7.32 (m, 1H), 7.15 (m, 1H), 6.38 (s, 1H), 5.35 (s, 2H), 2.45 (s, 3H), 2.43 (s, 3H). Mass spectrum (apci) m/z=344.0 (M+H-HCl).

Workup

  1. stirringthe reaction mixture was stirred for 15 minutes
  2. stirringthe reaction mixture was stirred for 15 minutes
  3. extractionthe reaction mixture was extracted with CH2Cl2
  4. customThe organic layer was purified by silica gel (10-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-92e402e0b7974ddca705c488a6a6ea02
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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