Acetic Acid → 1-Acetyl-3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide

HRID 1867748Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1867748
C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:34](O)(=[O:36])[CH3:35].[Cl:38][C:39]1[C:40]([F:68])=[C:41]([NH:45][C:46]2[C:55]3[C:50](=[CH:51][C:52]([O:66][CH3:67])=[C:53]([CH2:56][N:57]([CH3:65])[C:58]4([C:62]([NH2:64])=[O:63])[CH2:61][NH:60][CH2:59]4)[CH:54]=3)[N:49]=[CH:48][N:47]=2)[CH:42]=[CH:43][CH:44]=1>ClCCl>[C:34]([N:60]1[CH2:61][C:58]([N:57]([CH2:56][C:53]2[CH:54]=[C:55]3[C:50](=[CH:51][C:52]=2[O:66][CH3:67])[N:49]=[CH:48][N:47]=[C:46]3[NH:45][C:41]2[CH:42]=[CH:43][CH:44]=[C:39]([Cl:38])[C:40]=2[F:68])[CH3:65])([C:62]([NH2:64])=[O:63])[CH2:59]1)(=[O:36])[CH3:35]

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579798103-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide

Produkt 1

HCID 579798861-Acetyl-3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamideAusbeute 51 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Diisopropylethylamine (0.11 ml, 0.63 mmol) and then HATU (95 mg, 0.25 mmol) were added to a solution of acetic acid (18 μl, 0.31 mmol) in dichloromethane (1 ml). After 10 minutes, the hydrochloride salt of 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide (100 mg, 0.21 mmol Example 74) was added and the mixture stirred overnight at room temperature. After removal of the solvent, the resulting product was dissolved in dimethylformamide and purified on preparative HPLC (standard basic conditions) to give the title product as a powder (52 mg, 51%); 1H NMR Spectrum: (CDCl3) 1.92 (d, 3H), 2.38 (s, 3H), 3.70 (d, 1H), 3.83 (d, 1H), 3.98 (s, 3H), 4.18-4.27 (m, 3H), 4.55 (d, 1H), 5.80 (brs, 1H), 6.94 (brs, 1H), 7.15 (m, 2H), 7.29 (s, 1H), 7.96 (brs, 2H), 8.34 (brs, 1H), 8.72 (s, 1H); Mass Spectrum: (M+H)+ 487.

Aufarbeitung

  1. customAfter removal of the solvent
  2. dissolutionthe resulting product was dissolved in dimethylformamide
  3. custompurified on preparative HPLC (standard basic conditions)

Quellen und Nachweise

ORD-Eintrag
ord-493c91973ecf4b8a9ecc49240a0247a4
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07632840B2

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