Sodium Chloride → HCID 178496351, compound

HRID 1014478Notes

Reaction equation

HRID 1014478 reaction equation
Cl.Cl[C:3]1[N:16]2[C:7](=[N:8][C:9]3[C:14]([C:15]2=[O:17])=[C:13]([F:18])[CH:12]=[CH:11][CH:10]=3)[C:6]2[CH:19]=[CH:20][N:21](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]=2[N:4]=1.[CH3:32][O:33][C:34]1[CH:35]=[C:36]2[C:40](=[CH:41][C:42]=1[NH2:43])[N:39]([C:44](=[O:48])[CH2:45][O:46][CH3:47])[CH2:38][CH2:37]2.[NH4+:49].[OH-].[Na+].[Cl-].[OH-].[K+].[OH-].[Na+]>C1COCC1.CCOC(C)=O>[F:18][C:13]1[CH:12]=[CH:11][CH:10]=[C:9]([NH:8][C:7]2[N:16]=[C:3]([NH:43][C:42]3[CH:41]=[C:40]4[C:36]([CH2:37][CH2:38][N:39]4[C:44](=[O:48])[CH2:45][O:46][CH3:47])=[CH:35][C:34]=3[O:33][CH3:32])[NH:4][C:5]3=[N:21][CH:20]=[CH:19][C:6]=23)[C:14]=1[C:15]([NH2:49])=[O:17]

Participants

9

Reactant 6

HCID 5234Sodium ChlorideHCID 14797Potassium HydroxideHCID 14798Sodium HydroxideHCID 14923Ammonium HydroxideHCID 594417515-(methyloxy)-1-[(methyloxy)acetyl]-2,3-dihydro-1H-indol-6-amineHCID 673162535-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one HCl salt

Product 1

HCID 178496351HCID 178496351, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

A thick white slurry of 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one hydrogen chloride (400 mg, 0.835 mmol) and 5-(methyloxy)-1-[(methyloxy)acetyl]-2,3-dihydro-1H-indol-6-amine (197 mg, 0.835 mmol) in THF (15 mL) was heated at 80° C. for 17 h, cooled, then diluted with THF (20 mL) and a 30% aqueous NH4OH solution (50 mL). The reaction mixture was maintained for 17 h, then diluted with EtOAc (50 mL) and a saturated NaCl solution (25 mL). The organic layer was washed with a saturated NaCl solution (3×50 mL), concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2. The crude product was triturated using Et2O, dissolved in dioxane (15 mL) and a 1N KOH solution (3.64 mL, 3.64 mmol) and then heated at 80° C. for 3 h. The resulting mixture was allowed to cool somewhat, diluted with EtOAc (100 mL) and a 2N NaOH solution (50 mL). The organic layer was washed with a 2N NaOH solution (2×50 mL), concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2 to obtain 2-fluoro-6-{[2-({5-(methyloxy)-1-[(methyloxy)acetyl]-2,3-dihydro-1H-indol-6-yl}amino)-1 H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzamide as a yellow solid (63 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.11 (t, J=8.15 Hz, 2H), 3.76 (s, 3H), 4.01 (t, J=8.33 Hz, 2H), 4.14 (s, 2H), 6.16-6.27 (m, 1H), 6.76-6.89 (m, 1H), 6.90-6.99 (m, 2H), 7.22-7.38 (m, 1H), 7.58 (s, 1H), 8.00 (s, 1H), 8.08 (s, 1H), 8.49 (d, J=8.42 Hz, 1H), 8.63 (s, 1H), 10.52 (s, 1H), 11.29 (s, 1H) a Me-O signal with 3 protons is missing, may overlap with water peak in sample; ESIMS (M+H)+=506.16.

Workup

  1. temperaturecooled
  2. temperatureThe reaction mixture was maintained for 17 h
  3. washThe organic layer was washed with a saturated NaCl solution (3×50 mL)
  4. concentrationconcentrated onto Celite
  5. custompurified by silica gel chromatography
  6. customThe crude product was triturated
  7. dissolutiondissolved in dioxane (15 mL)
  8. temperatureto cool somewhat
  9. washThe organic layer was washed with a 2N NaOH solution (2×50 mL)
  10. concentrationconcentrated onto Celite
  11. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-dfbfaf9b1c0c4cc9b3aaceb99e8d5e50
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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