Sodium Hydroxide → 4-Methyl-3-[({4-[(4-phenylquinazolin-2-yl)amino]phenyl}carbonyl)amino]benzoic acid

HRID 406818

Reaktionsgleichung

Reaktionsgleichung von HRID 406818
[C:1]1([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]([NH:17][C:18]3[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:27][C:28]1[CH:29]=[C:30]([CH:35]=[CH:36][C:37]=1[CH3:38])[C:31]([O:33]C)=[O:32].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH-].[Na+]>CN(C)C=O.ClCCl.CO.O1CCCC1>[CH3:38][C:37]1[CH:36]=[CH:35][C:30]([C:31]([OH:33])=[O:32])=[CH:29][C:28]=1[NH:27][C:22]([C:21]1[CH:20]=[CH:19][C:18]([NH:17][C:9]2[N:8]=[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)=[CH:26][CH:25]=1)=[O:23]

Komponenten

10

Edukt 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 337778Methyl 3-amino-4-methylbenzoateHCID 7764484-[(4-Phenylquinazolin-2-yl)amino]benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Produkt 1

HCID 250701624-Methyl-3-[({4-[(4-phenylquinazolin-2-yl)amino]phenyl}carbonyl)amino]benzoic acidAusbeute 86,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a stirred solution of 4-(4-phenylquinazolin-2-ylamino)benzoic acid (1.02 g, 2.99 mmol), prepared as described in Example 10, methyl 3-amino-4-methylbenzoate (496 mg, 3.01 mmol), and Hunig's base (1.57 mL, 9.01 mmol) in dimethylformamide (15 mL) was added HATU (1.14 g, 3.00 mmol). The stirred mixture was heated to 60° C. overnight, then cooled to rt. The reaction was diluted with dichloromethane and washed with 2 N aqueous sodium hydroxide. The organic layer was then dried over sodium sulfate and concentrated on a rotary evaporator. The residue was sonicated with acetonitrile and filtered to give a light yellow solid that was suspended in a mixture of methanol (22 mL) and tetrahydrofuran (11 mL). AlN aqueous solution of sodium hydroxide (11 mL) was added and the stirred mixture was heated to 70° C. for 3 h. The reaction mixture was cooled to rt, concentrated on a rotary evaporator and redissolved in water, which was then made acidic with 1 N aqueous hydrochloric acid until the pH of the solution reached 5. The precipitate that formed was collected and dried in vacuo to afford 4-methyl-3-[({4-[(4-phenylquinazolin-2-yl)amino]phenyl}carbonyl)amino]benzoic acid (1.23 g, 86%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 10.34 (s, 1H), 9.82 (s, 1H), 8.18 (d, 2H), 8.00 (d, 2H), 7.95 (s, 1H), 7.90-7.78 (m, 5H), 7.72 (dd, 1H), 7.66-7.64 (m, 3H), 7.42 (ddd, 1H), 7.36 (d, 1H), 2.31 (s, 3H). MS (EI) for C29H22N4O3: 475.3 (MH+).

Aufarbeitung

  1. temperaturecooled to rt
  2. washwashed with 2 N aqueous sodium hydroxide
  3. dry with materialThe organic layer was then dried over sodium sulfate
  4. concentrationconcentrated on a rotary evaporator
  5. customThe residue was sonicated with acetonitrile
  6. filtrationfiltered
  7. customto give a light yellow solid
  8. temperaturethe stirred mixture was heated to 70° C. for 3 h
  9. temperatureThe reaction mixture was cooled to rt
  10. concentrationconcentrated on a rotary evaporator
  11. dissolutionredissolved in water
  12. customThe precipitate that formed
  13. customwas collected
  14. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-ba101ce917fa4c079b9c66c3aa0dfedf
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754092B2

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