Carbon Tetrachloride → 7-chloro-N-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-amine

HRID 1796570Notes

Reaction equation

HRID 1796570 reaction equation
[CH:1]1([NH:6][C:7]2[CH:12]=[CH:11][N:10]3[N:13]=[C:14]([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)[C:15]([C:16]4[CH:21]=[CH:20][N:19]=[C:18]([NH:22][CH:23]5[CH2:27][CH2:26][CH2:25][CH2:24]5)[N:17]=4)=[C:9]3[CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C([Li])CCC.C(Cl)(Cl)(Cl)[Cl:41]>O1CCCC1>[Cl:41][C:11]1[N:10]2[N:13]=[C:14]([C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)[C:15]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH:22][CH:23]4[CH2:24][CH2:25][CH2:26][CH2:27]4)[N:17]=3)=[C:9]2[CH:8]=[C:7]([NH:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)[CH:12]=1

Participants

5

Reactant 3

HCID 5943Carbon TetrachlorideHCID 10276099N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)-pyrazolo[1,5-a]pyridin-5-amineHCID 178418339Butyllithium

Product 1

HCID 102282547-chloro-N-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-amine (120 mg, 0.26 mmol) in tetrahydrofuran (5 mL) at −78 ° C. was added n-butyllithium (0.8 mL, 1.3 mmol of 1.6 M solution in hexanes). The resulting reaction was stirred at −78° C. for 10 minutes, then carbon tetrachloride (1 mL) was added. The reaction mixture was allowed to warm to room temperature and then quenched by the addition of water. The phase were separated and the organic phase dried over magnesium sulfate, filtered and concentrated. The resulting residue was purified by flash chromatography (1:1 hexanes-ethyl acetate) to give 7-chloro-N-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-amine (12 mg) as a foam. 1H-NMR (CDCl3): δ 7.97 (d, 1H), 7.62 (q, 2H), 7.44 (d, 1H), 7.15 (t, 2H), 6.48 (d, 1H), 6.22 (d, 1H), 5.30 (broad s, 1H), 4.44 (m, 1H), 4.18 (m, 1H), 3.94 (m, 1H), 1.4–2.1 (16H);19F-NMR (CDCl3): δ −113.24; MS m/z 492 (M+1).

Workup

  1. customThe resulting reaction
  2. temperatureto warm to room temperature
  3. customquenched by the addition of water
  4. customThe phase were separated
  5. dry with materialthe organic phase dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by flash chromatography (1:1 hexanes-ethyl acetate)

Sources & evidence

ORD record
ord-212df3962b05414780879cc1870cc5a0
Source dataset
uspto-grants-2006_04
Patent number
US07030134B2

Reaction notes

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