Acetic Acid → HCID 16737671, compound

HRID 2075137Notes

Reaction equation

HRID 2075137 reaction equation
[CH:1]1([C:7]2[CH:8]=[CH:9][C:10]3[O:14][C:13]([C:15]4[CH:22]=[CH:21][C:18]([CH:19]=O)=[CH:17][CH:16]=4)=[CH:12][C:11]=3[CH:23]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(=O)C.[NH:28]1[CH2:33][CH2:32][CH:31]([C:34]([OH:36])=[O:35])[CH2:30][CH2:29]1.C([BH3-])#N.[Na+]>C(Cl)Cl.CO.CS(C)=O>[CH:1]1([C:7]2[CH:8]=[CH:9][C:10]3[O:14][C:13]([C:15]4[CH:16]=[CH:17][C:18]([CH2:19][N:28]5[CH2:33][CH2:32][CH:31]([C:34]([OH:36])=[O:35])[CH2:30][CH2:29]5)=[CH:21][CH:22]=4)=[CH:12][C:11]=3[CH:23]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 37734-Piperidinecarboxylic acidHCID 5003444Sodium cyanoborohydrideHCID 59595913HCID 59595913, compound

Product 1

HCID 16737671HCID 16737671, compoundYield 52.7%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A mixture of 4-(5-cyclohexylbenzofuran-2-yl)benzaldehyde (22 mg, 0.07 mmol), acetic acid (7 μL, 0.11 mmol) and piperidine-4-carboxylic acid (14 mg, 0.11 mmol) in DCM/MeOH (1:1, 1.6 mL) was stirred at room temperature for 1 h. Sodium cyanoborohydride (2.3 mg, 0.05 mmol) was added and the reaction mixture was stirred for 4 h at room temperature. After concentration of solvent under reduced pressure, the resulting residue was dissolved in DMSO, filtered 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 (15.4 mg, 51%) [hS1P1 EC50=1600 nM, >25000 nM]: >95% purity by LCMS, ESI-MS: 418.1 (M+H)+, 1H NMR (400 MHz, CD3OD) δ 8.00 (d, J=8.0 Hz, 2H), 7.59 (d, J=8.0 Hz, 2H), 7.45 (d, J=1.6 Hz, 1H), 7.43 (d, J=8.4 Hz, 1H), 7.26 (s, 1H), 7.21 (dd, J=8.4 Hz, J=1.6 Hz), 4.35 (s, 2H), 3.57 (d, J=11.6 Hz, 2H), 3.07 (t, J=12 Hz, 2H), 2.64-2.53 (m, 2H), 2.24 (d, 2H), 1.19-1.86 (m, 4H), 1.79 (t, 2H), 1.58-1.42 (m, 4H), 1.38-1.26 (m, 2H).

Workup

  1. stirringthe reaction mixture was stirred for 4 h at room temperature
  2. filtrationfiltered
  3. custompurified by reverse phase preparative HPLC (Phenomenex reverse phase Luna 5μ C18(2) column, 60×21.2 mm ID)

Sources & evidence

ORD record
ord-e8a349c0e7524b2197a0b59d5e266ad3
Source dataset
uspto-grants-2011_04
Patent number
US07919519B2

Reaction notes

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