Acetic Acid → HCID 90011067, compound

HRID 929892Notes

Reaction equation

HRID 929892 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([N:16]3[CH2:19][CH:18]([C:20]4[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=4)[CH2:17]3)=[O:15])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[CH:26]1([CH:31]=O)[CH2:30][CH2:29][CH2:28][CH2:27]1.C(O)(=O)C.C([BH3-])#N>CO>[CH:26]1([CH2:31][N:1]2[CH2:6][CH2:5][CH:4]([C:7]3[CH:8]=[CH:9][C:10]([NH:13][C:14]([N:16]4[CH2:19][CH:18]([C:20]5[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=5)[CH2:17]4)=[O:15])=[CH:11][CH:12]=3)[CH2:3][CH2:2]2)[CH2:30][CH2:29][CH2:28][CH2:27]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 70106CyclopentanecarbaldehydeHCID 498716Cyano-borohydrideHCID 90011230HCID 90011230, compound

Product 1

HCID 90011067HCID 90011067, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
70 °C

Procedure

In a 20 mL vial was added N-(4-(piperidin-4-yl)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide, bistrifluoroacetic acid (67 mg, 0.12 mmol) dissolved in methanol, (2.0 mL) followed by the addition of cyclopentanecarbaldehyde (13 mg, 0.13 mmol) dissolved in methanol (0.45 mL), followed by the addition of acetic acid neat (68 μL, 1.2 mmol). The reaction mixture was shaken for 1 hour at 70° C. After that, MP-cyanoborohydride (272 mg, 2-3 mmol/g) resin was added and the resulting mixture was shaken at 70° C. overnight. The reaction mixture was filtered and concentrated to dryness. The residues were dissolved in 1:1 DMSO/methanol and purified by reverse phase chromoatography. 1H NMR (500 MHz, pyridine/d5-D2O Temp=90° C.) δ ppm 8.55 (dd, J=4.73, 1.68 Hz, 1 H) 8.40-8.48 (m, 1 H) 7.75 (d, J=8.54 Hz, 2 H) 7.56-7.61 (m, 1 H) 7.21 (d, J=8.54 Hz, 2 H) 7.16-7.19 (m, 1 H) 4.46 (t, J=8.24 Hz, 2 H) 4.10 (dd, J=8.09, 5.95 Hz, 2 H) 3.64-3.74 (m, 1 H) 3.28 (d, 2 H) 2.39-2.66 (m, 5 H) 2.02-2.26 (m, 3 H) 1.75-1.88 (m, 4 H) 1.40-1.59 (m, 4 H) 1.20-1.31 (m, 2 H); (ESI) m/z 419 (M+H).

Workup

  1. stirringthe resulting mixture was shaken at 70° C. overnight
  2. filtrationThe reaction mixture was filtered
  3. concentrationconcentrated to dryness
  4. dissolutionThe residues were dissolved in 1:1 DMSO/methanol
  5. custompurified by reverse phase chromoatography

Sources & evidence

ORD record
ord-f0d2801edd7e4b56980585cbc4a3d86e
Source dataset
uspto-grants-2016_03
Patent number
US09296723B2

Reaction notes

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