Ammonium Hydroxide → HCID 178491210, compound

HRID 1014556Notes

Reaction equation

HRID 1014556 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:47][CH3:48])=[CH:35][C:36]([CH3:46])=[C:37]([NH:39][C:40](=[O:45])[CH2:41][N:42]([CH3:44])[CH3:43])[CH:38]=1.[OH-].[NH4+:50]>FC(F)(F)CO.C1COCC1.CCOC(C)=O>[CH3:43][N:42]([CH3:44])[CH2:41][C:40]([NH:39][C:37]1[C:36]([CH3:46])=[CH:35][C:34]([O:47][CH3:48])=[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]([NH2:50])=[O:17])[N:16]=2)[CH:38]=1)=[O:45]

Participants

7

Reactant 3

HCID 14923Ammonium HydroxideHCID 59441883N1-[5-amino-2-methyl-4-(methyloxy)phenyl]-N2,N2-dimethylglycinamideHCID 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 178491210HCID 178491210, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
60 °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 (375 mg, 0.782 mmol) in 2,2,2-trifluoroethanol (10 mL) was added N1-[5-amino-2-methyl-4-(methyloxy)phenyl]-N2,N2-dimethylglycinamide (204 mg, 0.861 mmol). The resulting mixture was let stir at 60° C. for 45 min. Solvents were removed under reduced pressure to afford a green residue. Half of this material was dissolved in THF (10 mL) and aqueous ammonium hydroxide (27%) (30 mL, excess) was added. After stirring at rt for ˜36 h, the reaction was diluted with EtOAc and the organic layer was washed with water and a saturated brine solution and dried over sodium sulfate. Solvents were removed under reduced pressure. The residue was dissolved in dioxane (6 mL) in a microwave safe vessel and 2N NaOH (4 mL) was added. The reaction was then heated in a microwave at 120° C. for 15 min and then diluted with EtOAc. 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 to afford 2-[(2-{[5-[(N,N-dimethylglycyl)amino]-4-methyl-2-(methyloxy)phenyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluorobenzamide (52 mg, 0.103 mmol) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.17 (s, 3 H) 2.32 (s, 6 H) 3.03 (s, 2 H) 3.84 (s, 3H) 6.25 (dd, J=3.30, 1.65 Hz, 1 H) 6.86-6.97 (m, 2 H) 6.97-7.03 (m, 1 H) 7.40-7.49 (m, 1 H) 7.52 (s, 1 H) 8.04 (br. s., 1 H) 8.11 (s, 1 H) 8.16 (s, 1 H) 8.47 (d, J=8.42 Hz, 1 H) 9.19 (s, 1 H) 10.53 (s, 1 H) 11.37 (br. s., 1 H). ESIMS (M+H)+=507.

Workup

  1. customSolvents were removed under reduced pressure
  2. customto afford a green residue
  3. stirringAfter stirring at rt for ˜36 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. dissolutionThe residue was dissolved in dioxane (6 mL) in a microwave safe vessel
  8. addition2N NaOH (4 mL) was added
  9. temperatureThe reaction was then heated in a microwave at 120° C. for 15 min
  10. additiondiluted with EtOAc
  11. washThe organic layer was washed with water
  12. dry with materiala saturated brine solution and dried over sodium sulfate
  13. customSolvents were removed under reduced pressure
  14. customthe residue purified by chromatography on SiO2

Sources & evidence

ORD record
ord-0043276a1d344441a8b65341265b3e95
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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