2-Chloro-6-fluorobenzoyl chloride → 2-Chloro-6-fluoro-N-[3-(3-{2-[(3-fluorophenyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]benzamide

HRID 1159891Notes

Reaction equation

HRID 1159891 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=4)[N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:31][C:32]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[C:33]=1[C:34](Cl)=[O:35]>C1COCC1>[Cl:31][C:32]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[C:33]=1[C:34]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=4)[N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)[CH:3]=1)=[O:35]

Participants

4

Reactant 2

HCID 27365472-Chloro-6-fluorobenzoyl chlorideHCID 595114034-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-(3-fluorophenyl)-2-pyrimidinamine

Product 1

HCID 595138072-Chloro-6-fluoro-N-[3-(3-{2-[(3-fluorophenyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]benzamideYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-(3-fluorophenyl)-2-pyrimidinamine (92 mg, 0.23 mmol) in 2 mL of THF, added 2-chloro-6-fluorobenzoyl chloride (48 mg, 0.27 mmol). The reaction was stirred for 30 min at rt and quenched by addition of polystyrene-trisamine resin (20 mg). The reaction was allowed to stir overnight. The reaction was treated with excess Et3N, filtered, and washed with THF. The filtrate was collected, reduced in vacuo, and upon treatment with DCM, a white solid formed. Filtration and washing with the solid with Et2O yielded the desired product as a white solid, 96 mg, 65% yield. 1H NMR (400 MHz, d6-DMSO): δ 10.89 (s, 1H); 9.78 (s, 1H); 8.84 (d, J=6 Hz, 1H); 8.30 (d, J=5 Hz, 1H); 8.00 (s, 1H); 7.77-7.23 (m, 2H); 7.55-7.33 (m, 7H); 7.22 (q, J=8 Hz, 1H); 7.11 (t, J=7 Hz, 1H); 6.69 (td, J=2, 8 Hz, 1H); 6.60 (d, J=5 Hz, 1H). HRMS calculated C30H20ClF2N6O [M+H]+ 553.1355, found 553.1360.

Workup

  1. customquenched by addition of polystyrene-trisamine resin (20 mg)
  2. stirringto stir overnight
  3. additionThe reaction was treated with excess Et3N
  4. filtrationfiltered
  5. washwashed with THF
  6. customThe filtrate was collected
  7. customupon treatment with DCM, a white solid formed
  8. filtrationFiltration
  9. washwashing with the solid with Et2O

Sources & evidence

ORD record
ord-9f4d6182889c4e8f99a7bd3e3bbb9138
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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