Formaldehyde → HCID 11518493、化合物

HRID 1027917ノート

反応式

HRID 1027917 の反応式
C=O.[Cl:3][C:4]1[C:5]([F:34])=[C:6]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:32][CH3:33])=[C:18]([O:21][C@H:22]4[CH2:27][CH2:26][NH:25][C@H:24]([C:28]([NH:30][CH3:31])=[O:29])[CH2:23]4)[CH:19]=3)[N:14]=[CH:13][N:12]=2)[CH:7]=[CH:8][CH:9]=1.[C:35](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.CC(O)=O.C(Cl)Cl>[Cl:3][C:4]1[C:5]([F:34])=[C:6]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:32][CH3:33])=[C:18]([O:21][C@H:22]4[CH2:27][CH2:26][N:25]([CH3:35])[C@H:24]([C:28]([NH:30][CH3:31])=[O:29])[CH2:23]4)[CH:19]=3)[N:14]=[CH:13][N:12]=2)[CH:7]=[CH:8][CH:9]=1

参加物

7

反応物 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2 回HCID 67238726(2S,4S)-4-[[4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxy-6-quinazolinyl]oxy]-N-methyl-2-piperidinecarboxamide

生成物 1

HCID 11518493HCID 11518493、化合物収率 65%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 21922555Acetic acid methylene chloride溶媒

実験手順

Molecular sieves (5 g) followed by aqueous formaldehyde (10 ml) were added to a stirred solution of (2S,4S)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-N-methylpiperidine-2-carboxamide (3.0 g, 6.52 mmol) in DCM-AcOH (100:10 ml) at room temperature. The reaction mixture was stirred for 1-2 minutes before solid sodium triacetoxyborohydride (2.77 g, 13.1 mmol) was added portionwise over 5 minutes. The reaction was essentially complete after all the sodium triacetoxyborohydride reducing agent had been added. DCM was added (100 ml) and the reaction was carefully neutralised with saturated aqueous NaHCO3(aq). The organic extract was washed with brine, dried (MgSO4) and concentrated to a yellow foam. The residue was purified by flash chromatography (silica gel, DCM-NH3/MeOH 2%) to give the title product as a white solid (2 g, 65%): 1H NMR Spectrum: (DMSO d6) 1.85-1.96 (m, 3H), 2.07 (m, 1H), 2.15 (s, 3H), 2.45-2.50 (m, 1H), 2.59 (d, 3H), 2.71 (m, 1H), 2.84 (m, 1H), 3.96 (s, 3H), 4.81 (m, 1H), 7.23 (s, 1H), 7.28 (t, 1H), 7.47-7.53 (m, 2H), 7.81 (s, 2H), 8.37 (s, 1H), 9.59 (s, 1H); Mass Spectrum: (M+H)+ 474.1.

後処理

  1. additionwas added portionwise over 5 minutes
  2. additionhad been added
  3. extractionThe organic extract
  4. washwas washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated to a yellow foam
  7. customThe residue was purified by flash chromatography (silica gel, DCM-NH3/MeOH 2%)

出典と根拠

ORDレコード
ord-63f9c243d27141cc82e2bf34938d0765
出典データセット
uspto-grants-2014_05
特許番号
US08735410B2

反応ノート

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