Dimethyl Disulfide → HCID 10151314, compound

HRID 1296711Notes

Reaction equation

HRID 1296711 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][CH:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)[N:18]=3)=[C:15]3[N:10]([CH:11]=[N:12][CH:13]=[CH:14]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C([N-]C(C)C)(C)C.[Li+].[CH3:37][S:38]SC>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][CH:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)[N:18]=3)=[C:15]3[N:10]([C:11]([S:38][CH3:37])=[N:12][CH:13]=[CH:14]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 12232Dimethyl DisulfideHCID 2724682Lithium diisopropylamideHCID 10172841HCID 10172841, compound

Product 1

HCID 10151314HCID 10151314, compoundYield 57.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a cold (−78° C.) solution of 4-[2-(3-chlorophenyl)pyrazolo[1,5-c]pyrimidin-3-yl]-N-cyclopentyl-2-pyrimidinamine (267 mg, 0.683 mmol) in tetrahydrofuran (8 mL) was added lithium diisopropylamide (12.8 mL, 0.16 M in tetrahydrofuran, 2.05 mmol, made from 5 mL n—BuLi (1.6 M in hexanes) and 1.19 mL diisopropylamine in 43.5 mL tetrahydrofuran at 0° C.) dropwise. The reaction mixture was stirred at −78° C. for 10 minutes followed by the addition of methyl disulfide (246 μL, 2.73 mmol). The resultant mixture was stirred at −78° C. for 10 minutes then quenched with water. Upon warming to room temperature, the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (4:1 to 3:1 hexanes:ethyl acetate) provided 4-[2-(3-chlorophenyl)-7-(methylthio)pyrazolo[1,5-c]pyrimidin-3-yl]-N-cyclopentylpyrimidin-2-amine (171 mg, 57%) as a white solid. Rf 0:10 (4:1 hexanes:ethyl acetate); 1H NMR (CDCl3) δ 8.12 (d, 1H), 7.99–7.91 (m, 2H), 7.73 (s,1H), 7.51 (d, 1H), 7.48–7.34 (m, 2H), 6.35 (d,1H), 5.19 (d, 1H), 4.30 (m, 1H), 2.76 (s, 3H), 2.05 (m, 2H), 1.82–1.50 (m, 6H); MS m/z 437 (M+1).

Workup

  1. customthen quenched with water
  2. temperatureUpon warming to room temperature
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-5a3eaac6fb324b459b38c10611dbb9de
Source dataset
uspto-grants-2007_07
Patent number
US07247626B2

Reaction notes

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