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

HRID 1867772Notes

Reaction equation

HRID 1867772 reaction equation
[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

Participants

7

Reactant 4

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

Product 1

HCID 579798583-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-1-isopropyl-N-methylazetidine-3-carboxamideYield 47.2%

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]-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.

Workup

  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)

Sources & evidence

ORD record
ord-9d969492a08f479aa571898f69beeff1
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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