Formaldehyde → 1-(Tert-butoxycarbonyl)-3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-3-carboxylic acid

HRID 1867755ノート

反応式

HRID 1867755 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([NH:17][CH2:18][C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][C:28]=2[O:29][CH3:30])[N:25]=[CH:24][N:23]=[C:22]3[NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[C:33]=2[F:39])([C:14]([OH:16])=[O:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C=O.[C:42](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(O)(=O)C.ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([N:17]([CH2:18][C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][C:28]=2[O:29][CH3:30])[N:25]=[CH:24][N:23]=[C:22]3[NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[C:33]=2[F:39])[CH3:42])([C:14]([OH:16])=[O:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

7

反応物 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2 回HCID 690457921-(Tert-butoxycarbonyl)-3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)amino]piperidine-3-carboxylic acid

生成物 1

HCID 690457481-(Tert-butoxycarbonyl)-3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-3-carboxylic acid収率 89.3%

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 6344Dichloromethane溶媒

実験手順

1-(tert-Butoxycarbonyl)-3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)amino]piperidine-3-carboxylic acid (Isomer 1) (400 mg, 0.71 mmol) was dissolved in 5% acetic acid in dichloromethane (25 ml) and 37% aqueous formaldehyde (5 ml) added. The mixture was stirred rapidly and sodium triacetoxyborohydride (151 mg, 0.71 mmol) added. Over a period of 5 hours a further 3 equivalents of sodium triacetoxyborohydride were added. The mixture was neutralized with saturated aqueous sodium hydrogen carbonate, the layers separated and the organic phased dried (MgSO4) and concentrated under reduced pressure. Column chromatography on silica, eluting with 10% ammonia in methanol/dichloromethane gave 1-(tert-butoxycarbonyl)-3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-3-carboxylic acid (Isomer 1) (364 mg, 85%) as a white solid; 1H NMR Spectrum: (DMSO d6 100° C.) 1.27 (s, 9H); 1.47 (m, 1H); 1.86 (m, 1H); 2.01 (m, 2H); 2.30 (s, 3H); 3.30 (m, 1H); 3.44 (m, 1H); 3.63 (d, 1H); 3.74 (d, 1H); 3.81 (d, 1H); 3.88 (d, 1H); 3.96 (s, 3H); 7.19 (s, 1H); 7.25 (t, 1H); 7.40 (t, 1H); 7.65 (m, 1H); 8.22 (s, 1H); 8.41 (s, 1H); Mass Spectrum: (M+H)+ 574.5.

後処理

  1. customthe layers separated
  2. dry with materialthe organic phased dried (MgSO4)
  3. concentrationconcentrated under reduced pressure
  4. washColumn chromatography on silica, eluting with 10% ammonia in methanol/dichloromethane

出典と根拠

ORDレコード
ord-cd2d0860462b491dba66535e2e5e828e
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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