2-Fluoro-4-(trifluoromethyl)benzoyl chloride → HCID 68520361, compound

HRID 1171026Notes

Reaction equation

HRID 1171026 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:15]([NH2:17])=[N:14][CH:13]=[N:12][C:11]=3[C:10](I)=[N:9]2)=[CH:4][C:3]=1[O:19][CH3:20].[F:21][C:22]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][C:23]=1[C:24](Cl)=[O:25]>ClCCl.N1C=CC=CC=1>[C:3]([OH:19])(=[O:25])[CH3:4].[NH2:17][C:15]1[C:16]2[N:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:24](=[O:25])[C:23]4[CH:27]=[CH:28][C:29]([C:31]([F:32])([F:33])[F:34])=[CH:30][C:22]=4[F:21])=[C:3]([O:19][CH3:20])[CH:4]=3)[N:9]=[CH:10][C:11]=2[N:12]=[CH:13][N:14]=1

Participants

5

Reactant 2

HCID 1455802-Fluoro-4-(trifluoromethyl)benzoyl chlorideHCID 68518721HCID 68518721, compound

Product 1

HCID 68520361HCID 68520361, compoundYield 47.2%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

1-(4-Amino-3-methoxyphenyl)-3-iodo-1H-pyrazolo[4,3-d]pyrimidin-7-amine (80 mg, 0.209 mmol) in dichloromethane (5 mL) and pyridine (0.5 mL) was cooled to 5° C. in an ice bath then 2-fluoro-4-(trifluoromethyl)benzoyl chloride (52 mg, 0.230 mmol) was added dropwise. The solution was warmed to ambient temperature for 30 minutes then the solvents were removed by evaporation. The residue was dissolved in methanol (10 mL), 10% palladium on carbon (50 mg) was added and the mixture was hydrogenated at atmospheric pressure and 60° C. for 1 hour. The catalyst was removed by filtration through a pad of diatomaceous earth then the filtrate was concentrated and the material purified by preparative reverse phase chromatography. Lyophilization yielded the title compound (25 mg) as a white solid: 1H NMR (DMSO-d6, 400 MHz) δ 9.98 (s, 1H), 8.32 (m, 3H), 7.99 (t, 1H), 7.89 (d, 1H), 7.75 (d, 1H), 7.32 (d, 1H), 7.18 (m, 1H), 6.7 (bs, 2H), 3.93 (s, 3H), 1.60 (s, 3H); RP-HPLC (Hypersil HS C18, 5 μm, 100 A, 250×4.6 mm; 5%-100% acetonitrile-0.05 M ammonium acetate over 25 min, 1 mL/min) tr 18.75 min; MS: MH+ 447.1, M−H+ 445.1

Workup

  1. customthe solvents were removed by evaporation
  2. dissolutionThe residue was dissolved in methanol (10 mL)
  3. addition10% palladium on carbon (50 mg) was added
  4. customThe catalyst was removed by filtration through a pad of diatomaceous earth
  5. concentrationthe filtrate was concentrated
  6. customthe material purified by preparative reverse phase chromatography

Sources & evidence

ORD record
ord-177a7638b37a4b6e8b99f76d92fc90e6
Source dataset
uspto-grants-2010_11
Patent number
US07829570B2

Reaction notes

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