Hydrochloric Acid → 5-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8,10-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one

HRID 1014480

Reaction equation

HRID 1014480 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:21][C:22]2[CH:30]=[C:29]([F:31])[CH:28]=[C:27]([F:32])[C:23]=2[C:24]([NH2:26])=[O:25])[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:47]2[C:42](=[CH:43][C:44]([O:49][CH3:50])=[C:45](N)[CH:46]=2)[CH2:41][CH2:40]1)=[O:38])[CH3:35].Cl.[I-].[K+]>FC(F)(F)CO.O1CCOCC1.ClCCl.C(=O)(O)[O-].[Na+]>[CH3:33][N:34]([CH3:35])[CH2:36][C:37]([N:39]1[C:47]2[C:42](=[CH:43][C:44]([O:49][CH3:50])=[C:45]([NH:3][C:2]3[N:26]4[C:4](=[N:21][C:22]5[C:23]([C:24]4=[O:25])=[C:27]([F:32])[CH:28]=[C:29]([F:31])[CH:30]=5)[C:5]4[CH:10]=[CH:9][N:8]([S:11]([C:14]5[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=5)(=[O:13])=[O:12])[C:6]=4[N:7]=3)[CH:46]=2)[CH2:41][CH2:40]1)=[O:38]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 534147641-(6-Amino-5-methoxy-2,3-dihydro-1H-indol-1-yl)-2-(dimethylamino)ethan-1-oneHCID 866441962-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-4,6-difluorobenzamide

Product 1

HCID 673166665-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8,10-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-oneYield 95.1%

Reagents, catalysts & solvents 4

HCID 6344DichloromethaneSolventHCID 64092,2,2-TrifluoroethanolSolventHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-4,6-difluorobenzamide (1.96 g, 4.1 mmol) in 2,2,2-trifluoroethanol (40 mL) was added 1-[(dimethylamino)acetyl]-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine (1.33 g, 5.33 mmol), hydrochloric acid as a 4.0M solution in dioxane (4.1 mL), and catalytic potassium iodide (<10 mg). The resulting slurry was stirred at 90° C. in a pressure vial for 40 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 saturated brine solution and dried over sodium sulfate. Solvents were removed under reduced pressure to afford a yellow solid that was purified via trituration from diethyl ether to afford 5-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8,10-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (2.63 g, 3.90 mmol) as a yellow solid. (ESIMS (M+H)+=675)

Workup

  1. dissolutionhad completely dissolved
  2. temperatureThe resulting solution was cooled to room temperature
  3. washThe organic layer was washed with water and saturated brine solution
  4. dry with materialdried over sodium sulfate
  5. customSolvents were removed under reduced pressure
  6. customto afford a yellow solid
  7. customthat was purified via trituration from diethyl ether

Sources & evidence

ORD record
ord-1b6fa16d9e634e25beb9d4c923639d72
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Linked notes

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