Tetrahydrofuran → N-{3-[3-(2-{[3-(1,3-oxazol-5-yl)phenyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(3-thienyl)acetamide

HRID 1157565Notes

Reaction equation

HRID 1157565 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]([C:30]5[O:34][CH:33]=[N:32][CH:31]=5)[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.C1COCC1.C1C=CC2N(O)N=NC=2C=1.[S:50]1[CH:54]=[CH:53][C:52]([CH2:55][C:56](O)=[O:57])=[CH:51]1>CC(N(C)C)=O>[O:34]1[C:30]([C:26]2[CH:25]=[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:56](=[O:57])[CH2:55][C:52]6[CH:53]=[CH:54][S:50][CH:51]=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:29]=[CH:28][CH:27]=2)=[CH:31][N:32]=[CH:33]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 234043-Thiophenacetic acidHCID 757711-HydroxybenzotriazoleHCID 577371674-[2-(3-Aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-[3-(1,3-oxazol-5-yl)phenyl]-2-pyrimidinamine

Product 1

HCID 68682568N-{3-[3-(2-{[3-(1,3-oxazol-5-yl)phenyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(3-thienyl)acetamideYield 47%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of 4-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-[3-(1,3-oxazol-5-yl)phenyl]-2-pyrimidinamine (50 mg, 0.112 mmol) in 5:1 THF:DMA (2 mL) was added HOBT (46 mg, 0.34 mmol), 0.28 g polystyrene-bound carbodiimide resin (280 mg, 0.34 mmol), and 3-thienylacetic acid (48 mg, 0.34 mmol). After stirring at rt for 48 h, excess Dowex 550A OH anion-exchange resin was added and the resulting mixture was allowed to stir overnight. The solids were then removed by vacuum filtration and rinsed with THF (25 mL) and MeOH (25 mL). The filtrate was concentrated under reduced pressure and purified by mass-guided prep LC (C18, 15% H20 (with 0.1% formic acid)/CH3OH to 100% CH3OH gradient) to afford the title compound (30 mg, 47%). 1H NMR (400 MHz, DMSO-d6) δ 3.65 (s, 2H), 6.51 (d, 1H, J=5.37 Hz), 7.07-7.12 (m, 2H), 7.23-7.48 (m, 7H), 7.55 (s, 1H), 7.68-7.76 (m, 2H), 7.89 (s, 1H), 8.20 (s, 1H), 8.27 (d, 1H, J=5.37 Hz), 8.38 (s, 1H), 8.50-8.51 (m, 1H), 8.81 (d, 1H, J=6.84 Hz), 9.73 (s, 1H), 10.28 (s, 1H). ES-LC/MS m/z=570 [M+H]+.

Workup

  1. stirringto stir overnight
  2. customThe solids were then removed by vacuum filtration
  3. washrinsed with THF (25 mL) and MeOH (25 mL)
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. custompurified by mass-guided prep LC (C18, 15% H20 (with 0.1% formic acid)/CH3OH to 100% CH3OH gradient)

Sources & evidence

ORD record
ord-c59ad7de128c45a1b9eff125fc09ec75
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

Loading…