Formaldehyde → HCID 53373968、化合物

HRID 1971903ノート

反応式

HRID 1971903 の反応式
Cl.Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:26][CH:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[CH:11][C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:15][CH:14]=1)[CH2:4][CH2:5][CH3:6].C=O.O.[C:36](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C(O)(=O)C.O.CCOC(C)=O.C([O-])(O)=O.[Na+]>[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:26][CH:27]2[CH2:32][CH2:31][N:30]([CH3:36])[CH2:29][CH2:28]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:17][CH:18]=1)[CH2:4][CH2:5][CH3:6]

参加物

9

反応物 4

HCID 712FormaldehydeHCID 962WaterHCID 5049666Sodium triacetoxyborohydrideHCID 67375293HCID 67375293、化合物

生成物 1

HCID 53373968HCID 53373968、化合物

試薬・触媒・溶媒 4

HCID 176Acetic Acid触媒HCID 6344Dichloromethane溶媒HCID 516892Sodium Bicarbonate溶媒HCID 22728543Water ethylacetate溶媒

実験手順

To a solution of 3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (0.2 mmol, 82 mg) in DCM (2 mL) was added formaldehyde solution in water (37%, 2 mmol, 0.2 mL), and 1 drop of acetic acid. Then sodium triacetoxyborohydride (2 mmol, 424 mg) was added, and the mixture was stirred at room temperature for 0.5 hour then condensed. It was then diluted with water/EtOAc and neutralized with NaHCO3 powder. The organic layers were combined and dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH) to provide 3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(1-methyl-piperidin-4-yloxy)-pyridazine. The solid was dissolved in 1 mL DCM, 2N HCl in ether (1 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (79 mg). LCMS: m/z 425 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.78 and 7.86 (1H, s), 7.45-7.50 (2H, m), 7.11-7.15 (2H, m), 5.35-5.53 (1H, m), 4.42-4.49 (1H, m), 3.24-3.69 (4H, m), 3.12-3.17 (2H, m), 2.94 (3H, s), 1.90-2.58 (6H, m), 1.78-1.86 (2H, m), 1.34-1.64 (8H, m), 1.25-1.32 (2H, m), 0.82 (3H, t).

後処理

  1. customcondensed
  2. dry with materialdried over Na2SO4
  3. customThe solvent was removed in vacuo
  4. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH)

出典と根拠

ORDレコード
ord-185ba0f12dd04f849f60fa991a6993d2
出典データセット
uspto-grants-2013_04
特許番号
US08431575B2

反応ノート

読み込み中…