Carbon Tetrachloride → HCID 18446625, compound

HRID 1269054Notes

Reaction equation

HRID 1269054 reaction equation
[CH:1]1([NH:4][C:5]2[N:10]=[C:9]([C:11]3[C:12]([C:20]4[CH:25]=[CH:24][N:23]=[C:22]([NH:26][CH:27]([CH3:29])[CH3:28])[CH:21]=4)=[N:13][N:14]4[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=34)[CH:8]=[CH:7][N:6]=2)[CH2:3][CH2:2]1.C([Li])CCC.C(Cl)(Cl)(Cl)[Cl:36]>O1CCCC1>[Cl:36][C:19]1[N:14]2[N:13]=[C:12]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]([NH:26][CH:27]([CH3:29])[CH3:28])[CH:21]=3)[C:11]([C:9]3[CH:8]=[CH:7][N:6]=[C:5]([NH:4][CH:1]4[CH2:3][CH2:2]4)[N:10]=3)=[C:15]2[CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 5943Carbon TetrachlorideHCID 18446644HCID 18446644, compoundHCID 178418339Butyllithium

Product 1

HCID 18446625HCID 18446625, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a cold (−78° C.) solution of N-cyclopropyl-4-{2-[2-(isopropylamino)-4-pyridinyl]pyrazolo[1,5-a]pyridin-3-yl}-2-pyrimidinamine (178 mg, 0.462 mmol) in tetrahydrofuran (15 mL) was added n-butyllithium (866 μL, 1.6 M in hexanes, 1.39 mmol) dropwise. The reaction mixture was stirred at −78° C. for 30 minutes, then carbon tetrachloride (179 μL, 1.85 mmol) was added dropwise. The resultant mixture was warmed to room temperature and stirred 2 hours. The reaction mixture was quenched with water and diluted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate. Filtration and concentration provided crude 4-{7-chloro-2-[2-(isopropylamino)-4-pyridinyl]pyrazolo[1,5-a]pyridin-3-yl}-N-cyclopropyl-2-pyrimidinamine. This material was taken up in isopropylamine (3 mL, 35.2 mmol) and heated in a steel bomb at 120° C. for 16 hours. The reaction mixture was cooled and the excess isopropylamine was removed under a stream of nitrogen. Preparative HPLC provided 3-[2-(cyclopropylamino)-4-pyrimidinyl]-N-isopropyl-2-[2-(isopropylamino)-4-pyridinyl]pyrazolo[1,5-a]pyridin-7-amine (10 mg, 5%) as a yellow solid. 1H NMR (CDCl3) δ 8.10–8.07 (m, 2H), 7.87 (d, 1H), 7.35 (t, 1H), 6.85 (d, 1H), 6.69 (s, 1H), 6.51 (d, 1H), 6.06 (d, 1H), 5.94 (d, 1H), 5.68 (br, 1H), 4.16 (br, 1H), 3.93–3.79 (m, 2H), 2.85 (m, 1H), 1.40 (d, 6H), 1.25 (d, 6H), 0.87 (m, 2H), 0.64 (m, 2H); MS m/z 443 (M+1).

Workup

  1. stirringstirred 2 hours
  2. customThe reaction mixture was quenched with water
  3. additiondiluted 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-1a74509f57884310b6cec81cde054883
Source dataset
uspto-grants-2007_04
Patent number
US07199120B2

Reaction notes

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