Tris(hydroxymethyl)aminomethane → N-(3-{3-[2-(1,2,3,4-tetrahydro-7-isoquinolinylamino)-4-pyrimidinyl]-pyrazolo[1,5-a]pyridin-2-yl}phenyl)benzamide

HRID 1159899

Reaction equation

HRID 1159899 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)[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.N1[CH:36]=[CH:35][CH:34]=[C:33]([C:37](Cl)=[O:38])[CH:32]=1.[CH2:40](O)C(N)(CO)CO.[CH2:48]([N:50](CC)[CH2:51]C)[CH3:49]>C1COCC1>[CH2:51]1[C:26]2[C:27](=[CH:28][CH:29]=[C:24]([NH:23][C:19]3[N:18]=[C:17]([C:16]4[C:8]([C:4]5[CH:3]=[C:2]([NH:1][C:37](=[O:38])[C:33]6[CH:34]=[CH:35][CH:36]=[CH:40][CH:32]=6)[CH:7]=[CH:6][CH:5]=5)=[N:9][N:10]5[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=45)[CH:22]=[CH:21][N:20]=3)[CH:25]=2)[CH2:49][CH2:48][NH:50]1

Participants

6

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 8471TriethylamineHCID 82604Nicotinoyl chlorideHCID 595114034-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-(3-fluorophenyl)-2-pyrimidinamine

Product 1

HCID 59513880N-(3-{3-[2-(1,2,3,4-tetrahydro-7-isoquinolinylamino)-4-pyrimidinyl]-pyrazolo[1,5-a]pyridin-2-yl}phenyl)benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 100 mg (0.25 mmol) of 4-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-(3-fluorophenyl)-2-pyrimidinamine in THF at rt was added 63 mg (0.353 mmol) of 3-pyridinecarbonyl chloride. The reaction mixture was allowed to stir for 30 min. At this time, 3.0 eq of PS-Trisamine resin was added and the resulting slurry was allowed to stir overnight. Excess triethylamine was added and the resin was removed by filtration. The reaction mixture was concentrated to dryness and the product was triturated from DCM to give 20 mg of the title compound as a yellow solid: 1H-NMR (d6-DMSO, 400 MHz) δ 6.59 (d, 1H, J=5.5 Hz), 6.73 (td, 1H, J=7.9 and 2.5 Hz), 7.14 (td, 1H, J=7.0 and 1.5 Hz), 7.26 (dd, 1H, J=15.2 and 6.9 Hz), 7.35 (d, 1H, J=7.6 Hz), 7.45-7.58 (m, 4H), 7.80 (d, 1H, J=12.0 Hz), 7.95 (d, 1H, J=8.2 Hz), 8.10 (s, 1H), 8.29 (d, 1H, J=8.6 Hz), 8.32 (d, 1H, J=5.4 Hz), 8.50 (d, 1H, J=8.6 Hz), 8.76 (dd, 1H, J=4.7 and 1.5 Hz), 8.86 (d, 1H, J=7.1 Hz), 9.10 (s, 1H), 9.81 (s, 1H), and 10.57 (s, 1H); HRMS calcd for C29H20FN7O: 501.1713, found: 502.1801 (M+H+).

Workup

  1. stirringto stir overnight
  2. customthe resin was removed by filtration
  3. concentrationThe reaction mixture was concentrated to dryness
  4. customthe product was triturated from DCM

Sources & evidence

ORD record
ord-784a4f88b9c445a2916fda4dc287cbe0
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Linked notes

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