Carbon Tetrachloride → HCID 21948668, compound

HRID 1797069Notes

Reaction equation

HRID 1797069 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH:13]1([NH:18][C:19]2[N:24]=[C:23]([C:25]3[C:26]([C:44]4[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=4)=[N:27][N:28]4[CH:33]=[C:32]([C:34]([O:41][CH2:42][CH3:43])([O:38][CH2:39][CH3:40])[O:35][CH2:36][CH3:37])[CH:31]=[CH:30][C:29]=34)[CH:22]=[CH:21][N:20]=2)[CH2:17][CH2:16][CH2:15][CH2:14]1.C(Cl)(Cl)(Cl)[Cl:52]>O1CCCC1>[Cl:52][C:33]1[N:28]2[N:27]=[C:26]([C:44]3[CH:45]=[CH:46][C:47]([F:50])=[CH:48][CH:49]=3)[C:25]([C:23]3[CH:22]=[CH:21][N:20]=[C:19]([NH:18][CH:13]4[CH2:17][CH2:16][CH2:15][CH2:14]4)[N:24]=3)=[C:29]2[CH:30]=[CH:31][C:32]=1[C:34]([O:41][CH2:42][CH3:43])([O:38][CH2:39][CH3:40])[O:35][CH2:36][CH3:37]

Participants

6

Reactant 4

HCID 5943Carbon TetrachlorideHCID 7912DiisopropylamineHCID 22174844HCID 22174844, compoundHCID 178418339Butyllithium

Product 1

HCID 21948668HCID 21948668, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a cold (0° C.) solution of diisopropylamine (4.1 mL, 29 mmol) in tetrahydrofuran (25 mL) was added butyllithium (17 mL, 1.6 M in hexanes, 28 mmol) dropwise. The resultant solution was stirred at 0° C. for 10 minutes then cooled to −78° C. The reaction mixture was transferred via syringe to a cold (−78° C.) solution of N-cyclopentyl-4-[2-(4-fluorophenyl)-6-(triethoxymethyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine (4.86 g, 9.35 mmol) in tetrahydrofuran (25 mL). The reaction mixture was stirred at −78° C. for 30 minutes. Carbon tetrachloride (3.6 mL, 37 mmol) was added and the resulting mixture was warmed to room temperature and stirred for 2 hours. The reaction mixture was poured onto ice. After the ice had melted, the aqueous mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over sodium sulfate. Filtration and concentration followed by flash chromatography (4:1 hexanes:ethyl acetate) provided 4-[7-chloro-2-(4-fluorophenyl)-6-(triethoxymethyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (2.37 g, 46%) as a yellow solid. Rf 0.36 (4:1 hexanes:ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.36 (d, 1H), 8.08 (d, 1H), 7.85 (d, 1H), 7.67 (m, 2H), 7.15 (t, 2H), 6.33 (d, 1H), 5.15 (d, 1H), 4.36 (m, 1H), 3.46 (q, 6H), 2.10 (m, 2H), 1.81–1.53 (m, 6H), 1.26 (t, 9H); MS m/z 554 (M+1).

Workup

  1. temperaturethe resulting mixture was warmed to room temperature
  2. stirringstirred for 2 hours
  3. additionThe reaction mixture was poured onto ice
  4. extractionthe aqueous mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-53697c4f9e1d477cbfd8d26d088b6868
Source dataset
uspto-grants-2006_04
Patent number
US07034030B2

Reaction notes

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