Acetone → 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-1-isopropyl-N-methylazetidine-3-carboxamide

HRID 1867772Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1867772
[Cl:1][C:2]1[C:3]([F:32])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:30][CH3:31])=[C:16]([CH2:19][N:20]([CH3:29])[C:21]4([C:25]([NH:27][CH3:28])=[O:26])[CH2:24][NH:23][CH2:22]4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:33][C:34]([CH3:36])=O.C(N(C(C)C)CC)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.ClCCCl>[Cl:1][C:2]1[C:3]([F:32])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:30][CH3:31])=[C:16]([CH2:19][N:20]([CH3:29])[C:21]4([C:25]([NH:27][CH3:28])=[O:26])[CH2:24][N:23]([CH:34]([CH3:36])[CH3:33])[CH2:22]4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1

Komponenten

7

Edukt 4

HCID 180AcetoneHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 579798733-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-N-methylazetidine-3-carboxamide

Produkt 1

HCID 579798583-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-1-isopropyl-N-methylazetidine-3-carboxamideAusbeute 47,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 176Acetic AcidLösungsmittel

Versuchsvorschrift

The hydrochloride salt of 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-N-methylazetidine-3-carboxamide (110 mg, 0.22 mmol Example 99), acetone (23 μl, 0.31 mmol) and diisopropylethylamine (78 μl, 0.45 mmol) were stirred at room temperature in 5% acetic acid in 1,2-dichloroethane (2 ml) with 3 Å molecular sieves, and sodium triacetoxyborohydride (95 mg, 0.45 mmol) was added portionwise over 0.5 hours. After 2 hours, the reaction mixture was concentrated under reduced pressure. The resulting product was purified on preparative HPLC (standard basic conditions) to give the title product (52 mg, 47%) as a white powder; 1H NMR Spectrum: (CDCl3) 0.98 (d, 6H), 2.41 (s, 3H), 2.49 (m, 1H), 2.90 (s, 3H), 3.25 (brs, 2H), 3.57 (m, 2H), 3.96 (s, 2H), 3.97 (s, 3H), 7.16 (m, 2H), 7.24 (s, 1H), 7.57 (brs, 1H), 7.78 (brs, 1H), 8.00 (brs, 1H), 8.54 (brs, 1H), 8.73 (s, 1H); Mass Spectrum: (M+H)+ 501.

Aufarbeitung

  1. additionwas added portionwise over 0.5 hours
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. customThe resulting product was purified on preparative HPLC (standard basic conditions)

Quellen und Nachweise

ORD-Eintrag
ord-9d969492a08f479aa571898f69beeff1
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07632840B2

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