1,4-Dioxane hydrochloride → HCID 59441862, compound

HRID 1014519Notes

Reaction equation

HRID 1014519 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](N)=[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.[CH3:32][N:33]([CH2:35][C:36]([N:38]1[C:47]2[C:42](=[CH:43][C:44]([O:49][CH3:50])=[C:45]([NH2:48])[CH:46]=2)[CH2:41][CH2:40][CH2:39]1)=[O:37])[CH3:34].Cl.O1CCOCC1>C(O)C(F)(F)F.C1COCC1.[I-].[K+]>[CH3:32][N:33]([CH3:34])[CH2:35][C:36]([N:38]1[C:47]2[C:42](=[CH:43][C:44]([O:49][CH3:50])=[C:45]([NH:48][C:2]3[N:3]4[C:4](=[N:21][C:22]5[C:23]([C:24]4=[O:25])=[C:27]([F:31])[CH:28]=[CH:29][CH:30]=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:46]=2)[CH2:41][CH2:40][CH2:39]1)=[O:37]

Participants

7

Reactant 3

HCID 204431481,4-Dioxane hydrochlorideHCID 59442022HCID 59442022, compoundHCID 866441882-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide

Product 1

HCID 59441862HCID 59441862, compoundYield 68.7%

Reagents, catalysts & solvents 3

HCID 4875Potassium IodideCatalystHCID 64092,2,2-TrifluoroethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide (5.0 g, 10.87 mmol), 1-[(dimethylamino)acetyl]-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinamine (3.44 g, 13.05 mmol), and potassium iodide (0.090 g, 0.544 mmol) in trifluroethanol (250 ml) was added 4M HCl/dioxane (10.87 ml, 43.5 mmol). The reaction was heated overnight in a pressure vessel equipped with a threaded teflon cap. The reaction was diluted with THF (300 ml) and washed with saturated NaHCO3 (300 ml). The organic layer was removed, concentrated on rotovap, solids triturated from ethyl acetate/hexanes, and dried under house vacuum prior to next step to afford 5-{[1-(N,N-dimethylglycyl)-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinyl]amino}-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (5.0 g, 68%). ESIMS (M+H)+=670.

Workup

  1. temperatureThe reaction was heated overnight in a pressure vessel
  2. customcap
  3. washwashed with saturated NaHCO3 (300 ml)
  4. customThe organic layer was removed
  5. concentrationconcentrated on rotovap, solids
  6. customtriturated from ethyl acetate/hexanes
  7. customdried under house vacuum

Sources & evidence

ORD record
ord-86a8294300b341558f0455480375c652
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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