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

HRID 2404363Notes

Reaction equation

HRID 2404363 reaction equation
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]

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-181ee85849d041e6a8af0b349e8aac0f
Source dataset
uspto-grants-2014_08
Patent number
US08802704B2

Reaction notes

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