Acetic Acid → HCID 49835393, compound

HRID 2403226Notes

Reaction equation

HRID 2403226 reaction equation
[C:1]([BH3-])#[N:2].[Na+].[CH:5]1([N:11]2[C:15]([CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[C:14]([C:22]3[O:26][N:25]=[C:24]([C:27]4[CH:34]=[CH:33][C:30]([CH:31]=O)=[CH:29][CH:28]=4)[N:23]=3)[CH:13]=[N:12]2)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.[C:35]([OH:38])(=[O:37])[CH3:36]>CO>[CH:5]1([N:11]2[C:15]([CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[C:14]([C:22]3[O:26][N:25]=[C:24]([C:27]4[CH:28]=[CH:29][C:30]([CH2:31][NH:2][CH2:1][CH2:36][C:35]([OH:38])=[O:37])=[CH:33][CH:34]=4)[N:23]=3)[CH:13]=[N:12]2)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 86663316HCID 86663316, compound

Product 1

HCID 49835393HCID 49835393, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium cyanoborohydride (28 mg; 0.440 mmol) was added to a solution of 4-(5-(1-cyclohexyl-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde (163 mg; 0.40 mmol), obtained as described in Example 88, steps 1 and 2, and R-alanine (71.3 mg; 0.80 mmol) in methanol (3 mL) and acetic acid (69 μL; 1.20 mmol) and the mixture was stirred at room temperature overnight. The solvent was removed in vacuo and the residue purified by reverse-phase preparative HPLC. The residue was dissolved in methanol and loaded onto an SCX-2 column. The product was eluted with 0-20% NH3/methanol in DCM. The residue was then recrystallised from acetone to give Example 102 a white solid. 1H NMR: (Acetone-d6, 400 MHz) δ 7.99 (2 H, d, J=8.0 Hz), 7.94 (1 H, s), 7.46 (2 H, d, J=8.0 Hz), 4.46-4.37 (1 H, m), 3.92 (2 H, dd, J=11.5, 4.3 Hz), 3.84 (2 H, s), 3.75 (1 H, t, J=12.3 Hz), 3.43 (2 H, t, J=11.7 Hz), 2.82 (2 H, t, 6.0 Hz), 2.51-2.32 (4 H, m), 1.85-1.70 (6 H, m), 1.61 (1 H, d, J=12.9 Hz), 1.53 (2 H, d, J=12.9 Hz), 1.47-1.32 (2 H, m), 1.23-1.10 (1 H, m). LC/MS: 480 (M+H)+. HPLC (Method D) Rt 15.428 min (Purity: 99.4%).

Workup

  1. customobtained
  2. customThe solvent was removed in vacuo
  3. customthe residue purified by reverse-phase preparative HPLC
  4. dissolutionThe residue was dissolved in methanol
  5. washThe product was eluted with 0-20% NH3/methanol in DCM
  6. customThe residue was then recrystallised from acetone
  7. customto give Example 102 a white solid

Sources & evidence

ORD record
ord-96d0e3bc4ffd4a35a35521c3ba33f7d9
Source dataset
uspto-grants-2014_08
Patent number
US08802663B2

Reaction notes

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