Acetic Acid → HCID 72189916, compound

HRID 873564Notes

Reaction equation

HRID 873564 reaction equation
FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[NH:15]1[CH2:20][CH2:19][CH:18]([O:21][C:22]2[CH:27]=[CH:26][C:25]([NH:28][C:29]([CH:31]3[CH2:34][N:33]([C:35]4[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=4)[CH2:32]3)=[O:30])=[CH:24][CH:23]=2)[CH2:17][CH2:16]1.[CH:41]1([CH:44]=O)[CH2:43][CH2:42]1.C(O)(=O)C.C([BH3-])#N>CO>[CH:41]1([CH2:44][N:15]2[CH2:20][CH2:19][CH:18]([O:21][C:22]3[CH:23]=[CH:24][C:25]([NH:28][C:29]([CH:31]4[CH2:34][N:33]([C:35]5[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=5)[CH2:32]4)=[O:30])=[CH:26][CH:27]=3)[CH2:17][CH2:16]2)[CH2:43][CH2:42]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 123114CyclopropanecarboxaldehydeHCID 498716Cyano-borohydrideHCID 86702040HCID 86702040, compound

Product 1

HCID 72189916HCID 72189916, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
70 °C

Procedure

In a 20 mL vial was added N-(4-(piperidin-4-yloxy)phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide bis(2,2,2-trifluoroacetate) (67 mg, 0.12 mmol) dissolved in methanol (2.0 mL) followed by the addition of cyclopropanecarbaldehyde (10 mg, 0.14 mmol) dissolved in methanol (0.45 mL), followed by the addition of neat acetic acid (66 μL, 1.2 mmol). The mixture was shaken for 1 hour at 70° C. After that, 265 mg of MP-cyanoborohydride resin (2-3 mmol/g) was added and the resulting mixture was shaken at 70° C. overnight. The reaction mixture was filtered, checked by LC/MS and concentrated to dryness. The residues were dissolved in 1:1 DMSO/CH3OH and purified by reverse phase HPLC. 1H NMR (500 MHz, pyridine-d5/D2O) δ ppm 8.20-8.25 (m, 1 H) 8.13 (d, J=2.75 Hz, 1 H) 7.98-8.03 (m, 2 H) 7.11 (dd, J=8.24, 4.58 Hz, 1 H) 7.02-7.07 (m, 2 H) 6.72-6.78 (m, 1 H) 4.58 (d, J=2.75 Hz, 1H) 4.34 (t, J=6.71 Hz, 2 H) 4.05 (t, J=7.63 Hz, 2 H) 3.80-3.92 (m, 1 H) 3.34 (s, 4 H) 2.92 (d, J=7.32 Hz, 2 H) 2.32-2.44 (m, 2 H) 2.12 (s, 2 H) 1.09-1.22 (m, 1 H) 0.51-0.58 (m, 2 H) 0.28-0.34 (m, 2 H); MS (ESI(+)) m/e 407 (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/CH3OH
  5. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-cc96ae40d3da416faa8f3b0749fd3c0b
Source dataset
uspto-grants-2015_03
Patent number
US08975398B2

Reaction notes

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