Ammonium Hydroxide → HCID 178491111, compound

HRID 1014554Notes

Reaction equation

HRID 1014554 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.[NH2:32][C:33]1[C:34]([O:48][CH3:49])=[CH:35][C:36]([CH3:47])=[C:37]([N:39]([CH3:46])[C:40](=[O:45])[CH2:41][N:42]([CH3:44])[CH3:43])[CH:38]=1.[OH-].[NH4+:51]>FC(F)(F)CO.C1COCC1.C(OCC)(=O)C>[CH3:43][N:42]([CH3:44])[CH2:41][C:40]([N:39]([CH3:46])[C:37]1[C:36]([CH3:47])=[CH:35][C:34]([O:48][CH3:49])=[C:33]([NH:32][C:3]2[NH:4][C:5]3=[N:21][CH:20]=[CH:19][C:6]3=[C:7]([NH:8][C:9]3[CH:10]=[CH:11][CH:12]=[C:13]([F:18])[C:14]=3[C:15]([NH2:51])=[O:17])[N:16]=2)[CH:38]=1)=[O:45]

Participants

7

Reactant 3

HCID 14923Ammonium HydroxideHCID 59441685HCID 59441685, compoundHCID 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 178491111HCID 178491111, compound

Reagents, catalysts & solvents 3

HCID 64092,2,2-TrifluoroethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one HCl salt (0.5 g, 1.04 mmol) in 2,2,2-trifluoroethanol (10 mL) was added N1-[5-amino-2-methyl-4-(methyloxy)phenyl]-N1,N2,N2-trimethylglycinamide (0.275 g, 1.10 mmol). The resulting mixture was let stir at 50° C. for 90 min. Solvents were then removed under reduced pressure to afford a brown residue. Half of this material was then dissolved in THF (10 mL) and aqueous ammonium hydroxide (27%) (30 mL, excess) was added. After stirring at 30° C. for 24 h and rt for 18 h, the reaction was diluted with ethyl acetate and the organic layer was washed with water and a saturated brine solution and dried over sodium sulfate. Solvents were removed under reduced pressure and the residue purified by chromatography on SiO2. This material was dissolved in dioxane (6 mL) and 2N NaOH (4 mL) was added in a microwave safe vessel. The reaction was then heated in a microwave at 120° C. for 15 min. The reaction was diluted with EtOAc and the organic layer was washed with water and saturated brine solution and dried over sodium sulfate. Solvents were removed under reduced pressure and the residue purified by chromatography on SiO2 to afford 2-[(2-{[5-[(N,N-dimethylglycyl)(methyl)amino]-4-methyl-2-(methyloxy)phenyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluorobenzamide (95 mg, 0.182 mmol) as a light green solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.10 (s, 6 H) 2.13 (s, 3 H) 2.62 (d, J=15.57 Hz, 1 H) 2.83 (d, J=15.57 Hz, 1 H) 3.04 (s, 3 H) 3.91 (s, 3 H) 6.29 (dd, J=3.20, 1.74 Hz, 1 H) 6.91-7.00 (m, 2H) 7.00-7.07 (m, 1 H) 7.45 (d, J=6.78 Hz, 1 H) 7.54 (s, 1 H) 7.96-8.11 (m, 2 H) 8.23-8.34 (m, 2H) 10.38 (s, 1 H) 11.47 (br. s., 1 H). ESIMS (M+H)+=521.

Workup

  1. customSolvents were then removed under reduced pressure
  2. customto afford a brown residue
  3. stirringAfter stirring at 30° C. for 24 h and rt for 18 h
  4. washthe organic layer was washed with water
  5. dry with materiala saturated brine solution and dried over sodium sulfate
  6. customSolvents were removed under reduced pressure
  7. customthe residue purified by chromatography on SiO2
  8. dissolutionThis material was dissolved in dioxane (6 mL)
  9. addition2N NaOH (4 mL) was added in a microwave safe vessel
  10. temperatureThe reaction was then heated in a microwave at 120° C. for 15 min
  11. additionThe reaction was diluted with EtOAc
  12. washthe organic layer was washed with water and saturated brine solution
  13. dry with materialdried over sodium sulfate
  14. customSolvents were removed under reduced pressure
  15. customthe residue purified by chromatography on SiO2

Sources & evidence

ORD record
ord-cfdb2078bfc347bea571f8a8e7ec8088
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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