Trifluoroacetic acid → HCID 89784123, compound

HRID 1055849Notes

Reaction equation

HRID 1055849 reaction equation
[H-].[Na+].[NH2:3][C:4]1[CH:5]=[N:6][CH:7]=[N:8][CH:9]=1.Cl[C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[C:14]([C:21]3[NH:29][C:28]4[CH2:27][CH2:26][NH:25][C:24](=[O:30])[C:23]=4[CH:22]=3)[CH:15]=[CH:16][CH:17]=2)[N:12]=1.C(O)(C(F)(F)F)=O>CN(C=O)C.CS(C)=O>[N:6]1[CH:5]=[C:4]([NH:3][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[C:14]([C:21]4[NH:29][C:28]5[CH2:27][CH2:26][NH:25][C:24](=[O:30])[C:23]=5[CH:22]=4)[CH:15]=[CH:16][CH:17]=3)[N:12]=2)[CH:9]=[N:8][CH:7]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 344373Pyrimidin-5-amineHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89784123HCID 89784123, compoundYield 43.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To NaH (60 wt % in mineral oil; 0.071 g, 1.763 mmol) in 1 mL DMF was added 5-aminopyrimidine (AK Scientific, Union City, Calif.; 0.168 g, 1.76 mmol). After 10 min, 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 0.075 g, 0.252 mmol) was added and the reaction became dark red. After 2 h, the reaction was cooled to 0° C. and TFA (0.136 ml, 1.763 mmol) was added along with 1 mL DMSO. The reaction was filtered, and purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 10-60% ACN/H2O with 0.1% TFA); the product-containing fractions were concentrated in vacuo then treated with saturated aq. NaHCO3 and DCM. The organic layer was separated, and the aq. layer was extracted 3×DCM and 1× EtOAc. The combined organic layers were then treated with MeOH until the solid dissolved, dried over anhydrous MgSO4, filtered, and concentrated in vacuo to give 2-(2-(pyrimidin-5-ylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.039 g, 0.109 mmol, 43% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.66 (1H, br. s), 9.84 (1H, s), 9.21 (2H, s), 8.82 (1H, s), 8.21 (1H, d, J=8.8 Hz), 7.83 (1H, dd, J=7.2, 1.6 Hz), 7.70 (1H, dd, J=8.0, 1.6 Hz), 7.37 (1H, t, J=7.6 Hz), 7.15 (1H, d, J=8.8 Hz), 6.82-6.95 (1H, m), 6.66 (1H, d, J=2.2 Hz), 3.37-3.54 (2H, m), 2.83 (2H, t, J=6.9 Hz). m/z (ESI, +ve) 357.0 (M+H)+.

Workup

  1. waitAfter 2 h
  2. filtrationThe reaction was filtered
  3. custompurified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 10-60% ACN/H2O with 0.1% TFA)
  4. concentrationthe product-containing fractions were concentrated in vacuo
  5. additionthen treated with saturated aq. NaHCO3 and DCM
  6. customThe organic layer was separated
  7. extractionthe aq. layer was extracted 3×DCM and 1× EtOAc
  8. additionThe combined organic layers were then treated with MeOH until the solid
  9. dissolutiondissolved
  10. dry with materialdried over anhydrous MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-96536e2f405c4acdad945f444b534a03
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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