Hydrochloric Acid → HCID 59442045, compound

HRID 1014469Notes

Reaction equation

HRID 1014469 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[NH2:12])[N:8]([S:13]([C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)(=[O:15])=[O:14])[CH2:7][CH2:6]2.Cl[C:24]1[N:25]=[C:26]([NH:43][C:44]2[CH:52]=[CH:51][CH:50]=[C:49]([F:53])[C:45]=2[C:46]([NH2:48])=[O:47])[C:27]2[CH:32]=[CH:31][N:30]([S:33]([C:36]3[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][CH:37]=3)(=[O:35])=[O:34])[C:28]=2[N:29]=1.Cl.O1CCOCC1>FC(F)(F)CO.C([O-])(O)=O.[Na+]>[F:53][C:49]1[CH:50]=[CH:51][CH:52]=[C:44]([NH:43][C:26]2[C:27]3[CH:32]=[CH:31][N:30]([S:33]([C:36]4[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][CH:37]=4)(=[O:35])=[O:34])[C:28]=3[N:29]=[C:24]([NH:12][C:11]3[CH:10]=[C:9]4[C:5]([CH2:6][CH2:7][N:8]4[S:13]([C:16]4[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=4)(=[O:14])=[O:15])=[CH:4][C:3]=3[O:2][CH3:1])[N:25]=2)[C:45]=1[C:46]([NH2:48])=[O:47]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 59441716HCID 59441716, compoundHCID 866441882-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide

Product 1

HCID 59442045HCID 59442045, compound

Reagents, catalysts & solvents 2

HCID 64092,2,2-TrifluoroethanolSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 5-(methyloxy)-1-[(4-methylphenyl)sulfonyl]-2,3-dihydro-1H-indol-6-amine (4.0 g, 12.5 mmol), 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide (8.6 g, 18.79 mmol) and a 4 N solution of HCl in dioxane (16 mL, 62.5 mmol) in 2,2,2-trifluoroethanol (250 mL) was heated overnight in a sealed vessel at 80° C. The reaction mixture was diluted with a saturated NaHCO3 solution, and the resulting slurry was filtered and the solids were taken up into THF (1L). The resulting slurry was filtered and the filtrate was concentrated. The resulting orange solid was dissolved in THF (250 mL), and a 27% aqueous NH4OH solution (250 mL) was added and the reaction mixture was stirred overnight. The organic volatiles were evaporated, and the residue was extracted with CH2Cl2 (3×200 mL). The organic layers were combined, dried (Na2SO4), concentrated onto Celite and purified by silica gel chromatography using 0-2%THF/CH2Cl2 to obtain 2-fluoro-6-({2-({5-(methyloxy)-1-[(4-methylphenyl)sulfonyl]-2,3-dihydro-1H-indol-6-yl}amino)-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide as a yellow solid (2.8 g, 30% for 2 steps). ESIMS (M+H)+=742.17.

Workup

  1. filtrationthe resulting slurry was filtered
  2. filtrationThe resulting slurry was filtered
  3. concentrationthe filtrate was concentrated
  4. dissolutionThe resulting orange solid was dissolved in THF (250 mL)
  5. additiona 27% aqueous NH4OH solution (250 mL) was added
  6. customThe organic volatiles were evaporated
  7. extractionthe residue was extracted with CH2Cl2 (3×200 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated onto Celite
  10. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-8133f0a5b74c4fb0a5f754e0ef8251d0
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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