Acetic Acid → HCID 66795316, compound

HRID 2403228Notes

Reaction equation

HRID 2403228 reaction equation
C([BH3-])#N.[Na+].[CH:5]1([N:11]2[C:15]([CH2:16][O:17][CH3:18])=[C:14]([C:19]3[O:23][N:22]=[C:21]([C:24]4[CH:31]=[CH:30][C:27]([CH:28]=O)=[CH:26][CH:25]=4)[N:20]=3)[CH:13]=[N:12]2)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.[CH:32]([NH2:35])([CH3:34])[CH3:33].C(O)(=O)C>CO>[CH:5]1([N:11]2[C:15]([CH2:16][O:17][CH3:18])=[C:14]([C:19]3[O:23][N:22]=[C:21]([C:24]4[CH:25]=[CH:26][C:27]([CH2:28][NH:35][CH:32]([CH3:34])[CH3:33])=[CH:30][CH:31]=4)[N:20]=3)[CH:13]=[N:12]2)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6363IsopropylamineHCID 5003444Sodium cyanoborohydrideHCID 86663314HCID 86663314, compound

Product 1

HCID 66795316HCID 66795316, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium cyanoborohydride (18.0 mg; 0.286 mmol) was added to a solution of 4-(5-(1-cyclohexyl-5-(methoxymethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde (95.3 mg; 0.26 mmol) and isopropylamine (44.3 μL; 0.52 mmol) in methanol (3 mL) and acetic acid (47 μL; 0.78 mmol) and the mixture was stirred at room temperature overnight. The solvent was removed in vacuo and water (3 mL) was added and the product extracted into DCM (3×2 mL). The combined organic fractions were passed through a hydrophobic frit and the solvent removed in vacuo. The residue was purified by flash chromatography on a 12+M Biotage column, eluting with DCM containing increasing amounts of 5% methanol in DCM to give Example 121 as an off white solid. 1H NMR: (CDCl3, 400 MHz) δ 8.15-8.06 (3 H, m), 7.48 (2 H, d, J=7.8 Hz), 5.03 (2 H, s), 4.36-4.26 (1 H, m), 3.89 (2 H, s), 3.47 (3 H, m), 3.00-2.88 (1 H, m), 2.04-1.90 (6 H, m), 1.75 (1 H, d, J=12.3 Hz), 1.50-1.40 (2 H, m), 1.40-1.25 (1 H, m), 1.18 (6 H, d, J=6.4 Hz). LC/MS: 410 (M+H)+. HPLC (Method A) Rt 2.46 min (Purity: 99.0%).

Workup

  1. customThe solvent was removed in vacuo and water (3 mL)
  2. additionwas added
  3. extractionthe product extracted into DCM (3×2 mL)
  4. customthe solvent removed in vacuo
  5. customThe residue was purified by flash chromatography on a 12+M Biotage column
  6. washeluting with DCM containing
  7. temperatureincreasing amounts of 5% methanol in DCM
  8. customto give Example 121 as an off white solid

Sources & evidence

ORD record
ord-7e561a2e53234a99881e9c01b26ff9be
Source dataset
uspto-grants-2014_08
Patent number
US08802663B2

Reaction notes

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