Diisopropylamine → N-cyclopentyl-4-[2-isobutyl-7-(methylthio)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-amine

HRID 859972Notes

Reaction equation

HRID 859972 reaction equation
[CH:1]1([NH:6][C:7]2[N:12]=[C:11]([C:13]3[C:14]([CH2:22][CH:23]([CH3:25])[CH3:24])=[N:15][N:16]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=34)[CH:10]=[CH:9][N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.C(NC(C)C)(C)C.[CH3:46][S:47]SC>O1CCCC1.CCOCC.O>[CH:1]1([NH:6][C:7]2[N:12]=[C:11]([C:13]3[C:14]([CH2:22][CH:23]([CH3:25])[CH3:24])=[N:15][N:16]4[C:21]([S:47][CH3:46])=[CH:20][CH:19]=[CH:18][C:17]=34)[CH:10]=[CH:9][N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

9

Reactant 5

HCID 7912DiisopropylamineHCID 12232Dimethyl DisulfideHCID 2724682Lithium diisopropylamideHCID 10042600HCID 10042600, compoundHCID 178418339Butyllithium

Product 1

HCID 10339828N-cyclopentyl-4-[2-isobutyl-7-(methylthio)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-amine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a cold (−78° C.) solution of N-cyclopentyl-4(2-isobutylpyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine (750 mg, 2.23 mmol) in tetrahydrofuran (25 mL) was added lithium diisopropylamide (LDA) (11.18 mL of a 0.6 M stock solution was prepared from 18.75 mL of 1.6 M butyllithium and 4.20 mL of diisopropylamine in 27 mL of tetrahydrofuran, 6.71 mmol) dropwise. The reusitant solution was stirred at −78° C. for 15 minutes. Dimethyldisulfide (1.0 mL, 11.15 mmol) was added rapidly and the mixture was stirred for 1 hour. Water and ether were added and the layers separated. The organic layer was washed with brine. The aqueous layer was extracted with ether and the combined organics were dried over magnesium sulfate. Filtration and concentration followed flash chromatography on silica gel (2:1 hexane-ether) provided N-cyclopentyl-4-[2-isobutyl-7-(methylthio)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-amine. (712 mg, 84%) as a yellow solid. 1H NMR (CDCl3) δ 8.25 (d, 1H), 8.07 (d, 1H), 7.25 (t, 1H), 6.75 (d, 1H), 6.61 (d, 1H), 5.04 (d, 1H), 4.37 (m, 1H), 3.05 (d, 2H), 2.61 (s, 3H), 2.26–2.05 (m, 3H), 1.79–1.50 (m, 6H), 0.97 (d, 6H); MS m/z 382 (M+1).

Workup

  1. stirringthe mixture was stirred for 1 hour
  2. customthe layers separated
  3. washThe organic layer was washed with brine
  4. extractionThe aqueous layer was extracted with ether
  5. dry with materialthe combined organics were dried over magnesium sulfate
  6. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-bc2876a2aeea44738b7a6e096463c11e
Source dataset
uspto-grants-2006_12
Patent number
US07153863B2

Reaction notes

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