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

HRID 1867772ノート

反応式

HRID 1867772 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 176Acetic Acid溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-9d969492a08f479aa571898f69beeff1
出典データセット
uspto-grants-2009_12
特許番号
US07632840B2

反応ノート

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