2-Fluoro-4-(trifluoromethyl)benzoyl chloride → HCID 22346946, compound

HRID 897929Notes

Reaction equation

HRID 897929 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:20]3[CH2:25][CH2:24][N:23](C([O:28][C:29]([CH3:32])(C)C)=O)[CH2:22][CH2:21]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH2:17])=[C:13]([O:18][CH3:19])[CH:12]=3)[C:3]=12.[F:33][C:34]1[CH:42]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:40]=[CH:39][C:35]=1[C:36](Cl)=[O:37]>ClCCl.N1C=CC=CC=1>[C:29]([OH:37])(=[O:28])[CH3:32].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:20]3[CH2:21][CH2:22][NH:23][CH2:24][CH2:25]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:36](=[O:37])[C:35]4[CH:39]=[CH:40][C:41]([C:43]([F:44])([F:45])[F:46])=[CH:42][C:34]=4[F:33])=[C:13]([O:18][CH3:19])[CH:12]=3)[C:3]=12

Participants

5

Reactant 2

HCID 1455802-Fluoro-4-(trifluoromethyl)benzoyl chlorideHCID 22347369HCID 22347369, compound

Product 1

HCID 22346946HCID 22346946, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl 4-[4-amino-3-(4-amino-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate (0.10 g, 0.228 mmol) in dichloromethane (2 mL) and pyridine (1 mL) was treated with 2-fluoro-4-trifluoromethylbenzoyl chloride (0.057 g, 0.251 mmol) then stirred for 1 hour. The solvents were evaporated then the residue was treated with trifluoroacetic acid (1 mL) in dichloromethane (2 mL). The mixture was stirred for 1 hour at ambient temperature then the solvents were evaporated under reduced pressure and the residue purified by RP preparative HPLC on a C18 column using acetonitrile-0.05 M ammonium acetate as a mobile phase. Lyophilization afforded the pure title compound: 1H NMR (DMSO-d6, 400 MHz) δ 9.90 (d, 1H), 8.31 (d, 1H), 8.24 (s, 1H), 7.99 (t, 1H), 7.89 (d, 1H), 7.75 (d, 1H), 7.33 (s, 1H), 7.30 (d, 1H), 4.78 (m, 1H), 3.94 (s, 3H), 3.10 (m, 2H), 2.69 (m, 2H), 2.08 (m, 2H), 1.85-2.0 (m, 5H); RP-HPLC (Hypersil HS C18Hypersil 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 17.33 min; MS: MH+ 530.2.

Workup

  1. customThe solvents were evaporated
  2. additionthe residue was treated with trifluoroacetic acid (1 mL) in dichloromethane (2 mL)
  3. stirringThe mixture was stirred for 1 hour at ambient temperature
  4. customthe solvents were evaporated under reduced pressure
  5. customthe residue purified by RP preparative HPLC on a C18 column

Sources & evidence

ORD record
ord-053f25c4658e44f2a75f093e518d75e7
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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