Pyridine → HCID 22347075, compound

HRID 898046Notes

Reaction equation

HRID 898046 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12](Cl)=[O:13].N1C=CC=CC=1.[NH2:21][C:22]1[N:27]=[CH:26][N:25]=[C:24]2[N:28]([CH:40]3[CH2:45][CH2:44][C:43](=[O:46])[CH2:42][CH2:41]3)[N:29]=[C:30]([C:31]3[CH:36]=[CH:35][C:34]([NH2:37])=[C:33]([O:38][CH3:39])[CH:32]=3)[C:23]=12>ClCCl>[NH2:21][C:22]1[N:27]=[CH:26][N:25]=[C:24]2[N:28]([CH:40]3[CH2:45][CH2:44][C:43](=[O:46])[CH2:42][CH2:41]3)[N:29]=[C:30]([C:31]3[CH:36]=[CH:35][C:34]([NH:37][C:12](=[O:13])[C:3]4[CH:4]=[CH:5][C:6]([C:8]([F:11])([F:10])[F:9])=[CH:7][C:2]=4[F:1])=[C:33]([O:38][CH3:39])[CH:32]=3)[C:23]=12

Participants

5

Reactant 3

HCID 1049PyridineHCID 1455802-Fluoro-4-(trifluoromethyl)benzoyl chlorideHCID 22347344HCID 22347344, compound

Product 1

HCID 22347075HCID 22347075, compoundYield 68.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2-fluoro-4-trifluoromethyl-1-benzenecarbonyl chloride (0.87 g, 3.83 mmol) in dichloromethane (5 mL) was added into a mixture of pyridine (15 mL) and 4-[4-amino-3-(4-amino-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-cyclohexanone (1.00 g, 2.56 mmol) in dichloromethane (5 mL) at 0° C. over 5 minutes. The mixture was stirred at 0° C. for 10 minutes and at ambient temperature overnight. The solvent was removed under reduced pressure. The residue was partitioned between water and dichloromethane. The dichloromethane layer was washed with saturated aqueous ammonium chloride twice and saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and evaporated under reduced pressure to give a crude product. The crude product was purified by flash column chromatography on silica using Isco system to provide N1-{4-[4-amino-1-(4-oxocyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-trifluoromethylbenzamide (0.95 g, 1.76 mmol) as a white solid: 1H NMR (DMSO-d6, 400 MHz) δ 9.90 (dd, 1H), 8.30(d, 1H), 8.28 (s, 1H), 7.99 (t, 1H), 7.89 (d, 1H), 7.75 (d, 1H), 7.34 (s, 1H), 7.30 (d, 1H), 6.90 (br, 2H), 5.27 (m, 1H), 3.94 (s, 3H), 2.70 (m, 2H), 2.47 (m, 4H), 2.17 (m, 2H); RP-HPLC (Hitachi HPLC, Hypersil C18, 5 μm, 100 A, 250×4.6 mm; 25%-100% acetonitrile-0.05M ammonium acetate over 10 min, 1 mL/min) Rt 9.23 min. MS: MH+ 543.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customThe residue was partitioned between water and dichloromethane
  3. washThe dichloromethane layer was washed with saturated aqueous ammonium chloride twice
  4. dry with materialsaturated aqueous sodium chloride solution, dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customto give a crude product
  8. customThe crude product was purified by flash column chromatography on silica using Isco system

Sources & evidence

ORD record
ord-4504848c39a049caa7e8ec1c019d71d6
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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