4-Piperidinemethanol → (3-(4-((4-(Hydroxymethyl)piperidin-1-yl)methyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone

HRID 1035262Notes

Reaction equation

HRID 1035262 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][OH:8])[CH2:3][CH2:2]1.[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[O:21][C:20]([C:22]([N:24]3[CH2:27][CH:26]([O:28][C:29]4[CH:36]=[CH:35][C:32]([CH:33]=O)=[CH:31][CH:30]=4)[CH2:25]3)=[O:23])=[N:19][N:18]=2)=[CH:13][CH:12]=1.[Na].C([O-])(O)=O.[Na+]>ClCCl>[OH:8][CH2:7][CH:4]1[CH2:5][CH2:6][N:1]([CH2:33][C:32]2[CH:31]=[CH:30][C:29]([O:28][CH:26]3[CH2:27][N:24]([C:22]([C:20]4[O:21][C:17]([C:14]5[CH:15]=[CH:16][C:11]([O:10][CH3:9])=[CH:12][CH:13]=5)=[N:18][N:19]=4)=[O:23])[CH2:25]3)=[CH:36][CH:35]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 4207714-PiperidinemethanolHCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 580430894-(1-(5-(4-Methoxyphenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde

Product 1

HCID 56599191(3-(4-((4-(Hydroxymethyl)piperidin-1-yl)methyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Piperidin-4-ylmethanol (0.04 g, 0.35 mmol) was dissolved in dichloromethane (2 mL) and TEA (0.052 ml, 0.38 mmol) was added. Intermediate 55A (0.11 g, 0.29 mmol) was added followed by addition of sodium triacetoxyhydroborate (0.123 g, 0.58 mmol). The mixture was stirred at RT overnight. Dichloromethane (10 mL) and NaHCO3 (sat. 2 mL) were added and the mixture was filtered through a phase separator and the solvent was removed by evaporation. The product was purified by preparative reverse-phase HPLC at pH 10 to give 81 mg (58%). 1H NMR (600 MHz, DMSO) δ 1.05-1.17 (m, 2H), 1.28-1.39 (m, 1H), 1.57-1.66 (m, 2H), 1.82-1.92 (m, 2H), 2.75-2.84 (m, 2H), 3.19-3.27 (m, 3H), 3.83-3.92 (m, 3H), 4.06-4.13 (m, 1H), 4.37-4.45 (m, 1H), 4.5-4.67 (m, 2H), 5.04-5.19 (m, 2H), 6.85 (d, 2H), 7.16-7.27 (m, 4H), 8-8.05 (m, 2H), MS (APCI+) m/z 479 [M+H]+, LC-purity: 99%.

Workup

  1. filtrationthe mixture was filtered through a phase separator
  2. customthe solvent was removed by evaporation
  3. customThe product was purified by preparative reverse-phase HPLC at pH 10
  4. customto give 81 mg (58%)

Sources & evidence

ORD record
ord-f18a935cee03424991a0a7b73763abd2
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

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