Formaldehyde → 3-(((4-(3-Chloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yl)methyl)(methyl)amino)-1-methylazetidine-3-carboxamide

HRID 1867742Notes

Reaction equation

HRID 1867742 reaction equation
[Cl:1][C:2]1[C:3]([F:31])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:29][CH3:30])=[C:16]([CH2:19][N:20]([CH3:28])[C:21]4([C:25]([NH2:27])=[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.C=O.[C:34](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.ClCCCl>[Cl:1][C:2]1[C:3]([F:31])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:29][CH3:30])=[C:16]([CH2:19][N:20]([CH3:28])[C:21]4([C:25]([NH2:27])=[O:26])[CH2:24][N:23]([CH3:34])[CH2:22]4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 579798103-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide

Product 1

HCID 115326763-(((4-(3-Chloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yl)methyl)(methyl)amino)-1-methylazetidine-3-carboxamideYield 53%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolvent

Procedure

The hydrochloride salt of 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide Example 74 (100 mg, 0.19 mmol) and formaldehyde (51 μl of a 37% wt aqueous solution, 0.63 mmol) were stirred at room temperature in 5% acetic acid in 1,2-dichloroethane (2 ml) in the presence of 3 A molecular sieves. Sodium triacetoxyborohydride (89 mg, 0.42 mmol) was added portionwise over 0.5 hours. After the final addition the reaction mixture was concentrated under reduced pressure. The resulting product was purified on preparative HPLC (standard basic conditions) to give the title product (50 mg, 53%) as a white powder; 1H NMR Spectrum: (CDCl3) 2.41 (s, 3H), 2.45 (s, 3H), 3.35 (brs, 2H), 3.65 (d, 2H), 3.96-4.01 (m, 5H), 5.33 (brs, 1H), 7.15 (m, 2H), 7.25 (s, 1H), 7.47 (brs, 1H), 7.77 (brs, 1H), 7.98 (s, 1H), 8.55 (brs, 1H), 8.74 (s, 1H); Mass Spectrum: (M+H)+ 459.

Workup

  1. additionAfter the final addition the reaction mixture
  2. concentrationwas concentrated under reduced pressure
  3. customThe resulting product was purified on preparative HPLC (standard basic conditions)

Sources & evidence

ORD record
ord-bccb647f492a4bd78d00e75c39e13aa4
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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