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

HRID 2404363노트

반응식

HRID 2404363 반응식
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]

참가 물질

8

반응물 4

HCID 180AcetoneHCID 750GlycineHCID 5003444Sodium cyanoborohydride2회HCID 866615184-(5-(2'-Methyl-2-(trifluoromethyl)biphenyl-4-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde

생성물 1

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

시약·촉매·용매 3

HCID 176Acetic Acid용매2회HCID 887Methanol용매HCID 6344Dichloromethane용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-181ee85849d041e6a8af0b349e8aac0f
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08802704B2

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