Hydrochloric Acid → HCID 178486470, compound

HRID 1014524Notes

Reaction equation

HRID 1014524 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:21][C:22]2[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:23]=2[C:24]([NH2:26])=[O:25])[C:5]2[CH:10]=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:6]=2[N:7]=1.[C:32]([N:35]1[C:44]2[C:39](=[CH:40][C:41]([O:46][CH3:47])=[C:42]([NH2:45])[CH:43]=2)[CH2:38][CH2:37][CH2:36]1)(=[O:34])[CH3:33].Cl.C(=O)(O)[O-].[Na+].[OH-].[K+]>FC(F)(F)CO>[C:32]([N:35]1[C:44]2[C:39](=[CH:40][C:41]([O:46][CH3:47])=[C:42]([NH:45][C:2]3[NH:7][C:6]4=[N:8][CH:9]=[CH:10][C:5]4=[C:4]([NH:21][C:22]4[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:23]=4[C:24]([NH2:26])=[O:25])[N:3]=3)[CH:43]=2)[CH2:38][CH2:37][CH2:36]1)(=[O:34])[CH3:33]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 516892Sodium BicarbonateHCID 59442131HCID 59442131, compoundHCID 866441882-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide

Product 1

HCID 178486470HCID 178486470, compoundYield 12.6%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide (0.20 g, 0.44 mmol), 1-acetyl-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinamine (0.10 g mg, 0.43 mmol) was dissolved in 2,2,2-trifluoroethanol (10 mL) and hydrochloric acid (1.0 mL, 4.0 mmol, 4M in 1,4-dioxane) was added. The mixture was heated at 90° C. in a sealed tube for 24 h. The reaction was cooled, excess saturated aqueous sodium bicarbonate was added, and extracted with dichloromethane. The organic layer was separated, dried over magnesium sulfate, filtered, concentrated, diluted with tetrahydrofuran (35 mL) and treated with excess 27% aqueous ammonia (20 mL). The reaction was stirred in a sealed tube at 80° C. for 1 h, cooled, and the layers were separated. The organic layer was dried over sodium sulfate, concentrated, and purified by flash silica gel column chromatography (0 to 20% methanol /dichloromethane). “Pure” fractions were isolated, concentrated, dissolved in 1,4-dioxane (7.0 mL), treated with potassium hydroxide (4.0 mL, 20 mmol, 5M in water) and stirred for 24 h at 80° C. The reaction was cooled; the organic layer was separated, dried over sodium sulfate, and purified by flash silica gel column chromatography. Further purification via reverse phase HPLC (5 to 90% acetonitrile/water, 0.05% trifluoroacetic acid) provided 2-[(2-{[1-acetyl-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluorobenzamide (0.03 g, 91% pure, 0.054 mmol, 13% over 3 steps). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.81-1.91 (m, 2 H), 2.15 (s, 3 H), 2.68 (m, 2 H), 3.68 (t, J=6.1 Hz, 2 H), 3.86 (s, 3 H), 6.27 (s, 1 H), 6.85 (m, 1 H), 6.91-6.98 (m, 1 H), 7.02 (m, 1 H), 7.40-7.47 (m, 1 H), 7.52 (s, 1 H), 8.02 (bs, 1 H), 8.08 (bs, 1 H), 8.36-8.41 (m, 1 H), 8.46 (s, 1 H), 10.43 (s, 1 H), 11.44 (bs, 1H); ESIMS (M+H)+=490.

Workup

  1. temperatureThe reaction was cooled
  2. extractionextracted with dichloromethane
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additiondiluted with tetrahydrofuran (35 mL)
  8. additiontreated with excess 27% aqueous ammonia (20 mL)
  9. temperaturecooled
  10. customthe layers were separated
  11. dry with materialThe organic layer was dried over sodium sulfate
  12. concentrationconcentrated
  13. custompurified by flash silica gel column chromatography (0 to 20% methanol /dichloromethane)
  14. custom“Pure” fractions were isolated
  15. concentrationconcentrated
  16. dissolutiondissolved in 1,4-dioxane (7.0 mL)
  17. stirringstirred for 24 h at 80° C
  18. temperatureThe reaction was cooled
  19. customthe organic layer was separated
  20. dry with materialdried over sodium sulfate
  21. custompurified by flash silica gel column chromatography
  22. customFurther purification via reverse phase HPLC (5 to 90% acetonitrile/water, 0.05% trifluoroacetic acid)

Sources & evidence

ORD record
ord-96f6a6b517674859acef37fcf47d1a82
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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