Sodium Chloride → HCID 178486479, compound

HRID 1014551Notes

Reaction equation

HRID 1014551 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[C:19]([F:32])=[CH:20][N:21](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]=2[N:4]=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]([NH2:48])[CH:46]=2)[CH2:41][CH2:40]1)=[O:38])[CH3:35].[NH4+:51].[OH-].[Na+].[Cl-].[OH-].[K+].C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O>[CH3:35][N:34]([CH3:33])[CH2:36][C:37]([N:39]1[C:47]2[C:42](=[CH:43][C:44]([O:49][CH3:50])=[C:45]([NH:48][C:3]3[NH:4][C:5]4=[N:21][CH:20]=[C:19]([F:32])[C:6]4=[C:7]([NH:8][C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([F:18])[C:14]=4[C:15]([NH2:51])=[O:17])[N:16]=3)[CH:46]=2)[CH2:41][CH2:40]1)=[O:38]

Participants

9

Reactant 6

HCID 5234Sodium ChlorideHCID 14797Potassium HydroxideHCID 14923Ammonium HydroxideHCID 516892Sodium BicarbonateHCID 534147641-(6-Amino-5-methoxy-2,3-dihydro-1H-indol-1-yl)-2-(dimethylamino)ethan-1-oneHCID 67316036HCID 67316036, compound

Product 1

HCID 178486479HCID 178486479, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A yellow slurry of 5-chloro-1,8-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one hydrogen chloride (578 mg, 1.162 mmol) and 1-[(dimethylamino)acetyl]-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine (290 mg, 1.162 mmol) in THF (110 mL) was stirred at rt for 18 h. 80 mL of the resulting mixture was treated with a 27% aqueous NH4OH solution (100 mL). The reaction mixture was stirred at rt for 4 h. EtOAc (200 mL) and a saturated NaCl solution (50 mL) were added. The organic layer was washed with a saturated NaCl solution (2×100 mL), dried (Na2SO4) and concentrated. The residue was triturated with CH2Cl2 and Et2O. The crude intermediate was taken up into dioxane (10 mL) and treated with a 1N aqueous KOH solution (3 mL, 3.00 mmol). The reaction mixture was heated at 80° C. for 1 h. EtOAc (100 mL) and a saturated NaHCO3 solution (50 mL) were added. The organic layer was washed with a saturated NaCl solution (50 mL), concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2 to obtain 2-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-5-fluoro-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluorobenzamide as a pale yellow solid (80 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.25 (s, 6H), 3.06-3.25 (m, 4H), 3.75 (s, 3H), 4.18 (t, J=8.33 Hz, 2H), 6.75-6.94 (m, 2H), 6.98 (s, 1H), 7.18-7.34 (m, 1H), 7.84 (s, 1H), 8.05 (s, 1H), 8.14 (s, 1H), 8.45 (s, 1H), 8.60 (d, J=8.42 Hz, 1H), 10.26 (s, 1H), 11.02 (s, 1H); ESIMS (M+H)+=537.27.

Workup

  1. washThe organic layer was washed with a saturated NaCl solution (2×100 mL)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe residue was triturated with CH2Cl2 and Et2O
  5. temperatureThe reaction mixture was heated at 80° C. for 1 h
  6. washThe organic layer was washed with a saturated NaCl solution (50 mL)
  7. concentrationconcentrated onto Celite
  8. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-69817d82808747d78f2b7904bee19271
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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