Acetic Acid → HCID 16737504, compound

HRID 2075140Notes

Reaction equation

HRID 2075140 reaction equation
[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11]([C:13]3[CH:20]=[CH:19][C:16]([CH:17]=O)=[CH:15][CH:14]=3)=[CH:10][C:9]=2[CH:21]=1)[CH:2]([CH3:4])[CH3:3].C(O)(=O)C.[NH:26]1[CH2:29][CH:28]([C:30]([OH:32])=[O:31])[CH2:27]1.C([BH3-])#N.[Na+]>C(Cl)Cl.CO.CS(C)=O>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11]([C:13]3[CH:14]=[CH:15][C:16]([CH2:17][N:26]4[CH2:29][CH:28]([C:30]([OH:32])=[O:31])[CH2:27]4)=[CH:19][CH:20]=3)=[CH:10][C:9]=2[CH:21]=1)[CH:2]([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 931923-azetidinecarboxylic AcidHCID 5003444Sodium cyanoborohydrideHCID 59595889HCID 59595889, compound

Product 1

HCID 16737504HCID 16737504, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A mixture of 4-(5-isobutylbenzofuran-2-yl)benzaldehyde (30 mg, 0.11 mmol), acetic acid (10 μL, 0.15 mmol) and azetidine-3-carboxylic acid (16 mg, 0.16 mmol) in DCM/MeOH (1:1, 2 mL) was stirred at room temperature for 1 h. Sodium cyanoborohydride (3.4 mg, 0.054 mmol) was added and the reaction mixture was stirred for 3 h at room temperature. After concentration of solvent under reduced pressure, the resulting residue was dissolved in an aliquot of DMSO and purified by reverse phase preparative HPLC (Phenomenex reverse phase Luna 5μ C18(2) column, 60×21.2 mm ID) to yield the desired final product (25.6 mg, 65% yield) as a colorless film [hS1P1 EC50=270 nM, 490 nM, 383 nM]: >95% purity by LCMS, ESI-MS: 364.0 (M+H)+, 1H NMR (400 MHz, CD3OD) δ 7.99 (d, 2H), 7.55 (d, 2H), 7.42 (d, 1H), 7.39 (s, 1H), 7.24 (s, 1H), 7.12 (dd, 1H), 4.44 (s, 2H), 4.33 (d, 4H), 3.68 (m, 1H), 2.57 (d, 2H), 1.90 (m, 1H), 0.92 (d, 6H).

Workup

  1. stirringthe reaction mixture was stirred for 3 h at room temperature
  2. custompurified by reverse phase preparative HPLC (Phenomenex reverse phase Luna 5μ C18(2) column, 60×21.2 mm ID)

Sources & evidence

ORD record
ord-4d8f708760fc46bca9fc83ae2ef2848b
Source dataset
uspto-grants-2011_04
Patent number
US07919519B2

Reaction notes

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