Hydrochloric Acid → HCID 67315992, compound

HRID 1014497Notes

Reaction equation

HRID 1014497 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:21][C:22]2[C:27]([C:28](N)=[O:29])=[C:26]([F:31])[C:25]([F:32])=[CH:24][CH:23]=2)[C:5]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:6]=2[N:7]=1.[CH3:33][N:34]([CH2:36][C:37]([N:39]1[C:48]2[C:43](=[CH:44][C:45]([O:50][CH3:51])=[C:46]([NH2:49])[CH:47]=2)[CH2:42][CH2:41][CH2:40]1)=[O:38])[CH3:35].Cl.O1CCOCC1.[I-].[K+]>FC(F)(F)CO.ClCCl.C(=O)(O)[O-].[Na+]>[CH3:35][N:34]([CH3:33])[CH2:36][C:37]([N:39]1[C:48]2[C:43](=[CH:44][C:45]([O:50][CH3:51])=[C:46]([NH:49][C:2]3[N:3]4[C:4](=[N:21][C:22]5[C:27]([C:28]4=[O:29])=[C:26]([F:31])[C:25]([F:32])=[CH:24][CH:23]=5)[C:5]4[CH:10]=[CH:9][N:8]([S:11]([C:14]5[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=5)(=[O:13])=[O:12])[C:6]=4[N:7]=3)[CH:47]=2)[CH2:42][CH2:41][CH2:40]1)=[O:38]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 312751,4-DioxaneHCID 59442022HCID 59442022, compoundHCID 86644195HCID 86644195, compound

Product 1

HCID 67315992HCID 67315992, compoundYield 96%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 64092,2,2-TrifluoroethanolSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of 6-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-2,3-difluorobenzamide (600 mg, 1.26 mmol) in 2,2,2-trifluoroethanol (40 ml) was added 1-[(dimethylamino)acetyl]-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinamine (366 mg, 1.39 mmol), hydrochloric acid as a 4.0M solution in dioxane (2.51 ml, 10.1 mmol), and catalytic potassium iodide (<10 mg). The resulting slurry was stirred at 90° C. in a pressure vial for 24 hours, at which time all solids had completely dissolved. The resulting solution was cooled to room temperature and diluted with dichloromethane and saturated sodium bicarbonate as to adjust the aqueous layer to pH>10. The organic layer was washed with water and a saturated brine solution, dried over sodium sulfate, filtered and solvents were removed under reduced pressure. The resulting green solid was purified via trituration with diethyl ether to afford 5-{[1-(N,N-dimethylglycyl)-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinyl]amino}-8,9-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (830 mg, 1.21 mmol) as a yellow solid. (ESIMS (M+H)+=688)

Workup

  1. dissolutionhad completely dissolved
  2. temperatureThe resulting solution was cooled to room temperature
  3. washThe organic layer was washed with water
  4. dry with materiala saturated brine solution, dried over sodium sulfate
  5. filtrationfiltered
  6. customsolvents were removed under reduced pressure
  7. customThe resulting green solid was purified via trituration with diethyl ether

Sources & evidence

ORD record
ord-35a6a8586eba4ca4aab5c9b7d3e3387b
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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