Acetone → (Isopropyl-{4-[5-(2'-methyl-2-trifluoromethyl-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-amino)-acetic acid

HRID 2404363ノート

反応式

HRID 2404363 の反応式
C([BH3-])#N.[Na+].[CH3:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]1[CH:17]=[CH:16][C:15]([C:18]2[O:22][N:21]=[C:20]([C:23]3[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=3)[N:19]=2)=[CH:14][C:13]=1[C:31]([F:34])([F:33])[F:32].[NH2:35][CH2:36][C:37]([OH:39])=[O:38].[CH3:40][C:41]([CH3:43])=O>CO.CC(O)=O.C(Cl)Cl>[CH:41]([N:35]([CH2:36][C:37]([OH:39])=[O:38])[CH2:27][C:26]1[CH:25]=[CH:24][C:23]([C:20]2[N:19]=[C:18]([C:15]3[CH:16]=[CH:17][C:12]([C:7]4[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=4[CH3:5])=[C:13]([C:31]([F:32])([F:33])[F:34])[CH:14]=3)[O:22][N:21]=2)=[CH:30][CH:29]=1)([CH3:43])[CH3:40]

参加物

8

反応物 4

HCID 180AcetoneHCID 750GlycineHCID 5003444Sodium cyanoborohydride2 回HCID 866615184-(5-(2'-Methyl-2-(trifluoromethyl)biphenyl-4-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde

生成物 1

HCID 46931458(Isopropyl-{4-[5-(2'-methyl-2-trifluoromethyl-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-amino)-acetic acid

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒2 回HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

Sodium cyanoborohydride (18 mg, 0.28 mmol) was added to a solution of 4-(5-(2′-methyl-2-(trifluoromethyl)biphenyl-4-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde (0.25 mmol) and 2-aminoacetic acid (23 mg, 0.25 mmol) in a mixture of methanol (3 mL), DCM (3 mL) and acetic acid (38 μl). The mixture was stirred at room temperature overnight and was filtered through a frit under positive pressure. To the filtrate was added acetone (67 mg; 1.5 mmol) followed by addition of AcOH until the pH was in the range of 3-4 (240 mL). To the resulting mixture was added sodium cyanoborohydride (79 mg, 1.26 mmol), the mixture stirred for 16 hours, the solvent removed in vacuo and the residue purified by reverse phase HPLC to give a white solid as the title compound. 1H NMR (DMSO-d6, 400 MHz) δ 8.55-8.53 (1H, m), 8.53-8.48 (1H, m), 8.13-8.09 (2H, m), 7.71 (1H, d, J=7.9 Hz), 7.63 (2H, d, J=8.0 Hz), 7.37-7.34 (2H, m), 7.28-7.24 (1H, m), 7.15 (1H, d, J=7.5 Hz), 4.02 (2H, s), 3.24-3.22 (3H, m), 2.01 (3H, s), 1.11 (6H, d, J=6.5 Hz). LC/MS (Method A): 510 (M+H)+. HPLC (Method F) Rt=3.39 min (Purity: 99.1%).

後処理

  1. filtrationwas filtered through a frit under positive pressure
  2. stirringthe mixture stirred for 16 hours
  3. customthe solvent removed in vacuo
  4. customthe residue purified by reverse phase HPLC

出典と根拠

ORDレコード
ord-181ee85849d041e6a8af0b349e8aac0f
出典データセット
uspto-grants-2014_08
特許番号
US08802704B2

反応ノート

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