Sodium Bicarbonate → (3-(4-((3-(Hydroxymethyl)-3-methylpyrrolidin-1-yl)methyl)-2-methylphenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone

HRID 1035263Notes

Reaction equation

HRID 1035263 reaction equation
Cl.[CH3:2][C:3]1([CH2:8][OH:9])[CH2:7][CH2:6][NH:5][CH2:4]1.[CH3:10][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][C:18]=1[O:19][CH:20]1[CH2:23][N:22]([C:24]([C:26]2[O:27][C:28]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[N:29][N:30]=2)=[O:25])[CH2:21]1)[CH:14]=O.[Na].[C:38]([O-])(O)=[O:39].[Na+]>ClCCl.C1COCC1>[OH:9][CH2:8][C:3]1([CH3:2])[CH2:7][CH2:6][N:5]([CH2:14][C:13]2[CH:16]=[CH:17][C:18]([O:19][CH:20]3[CH2:23][N:22]([C:24]([C:26]4[O:27][C:28]([C:31]5[CH:32]=[CH:33][C:34]([O:39][CH3:38])=[CH:35][CH:36]=5)=[N:29][N:30]=4)=[O:25])[CH2:21]3)=[C:11]([CH3:10])[CH:12]=2)[CH2:4]1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 580430913-Methyl-4-(1-(5-Phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehydeHCID 66653455(3-Methylpyrrolidin-3-yl)methanol hydrochloride

Product 1

HCID 56599192(3-(4-((3-(Hydroxymethyl)-3-methylpyrrolidin-1-yl)methyl)-2-methylphenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Intermediate 84A (0.095 g, 0.63 mmol) was dissolved in dichloromethane (6 mL), THF (1 mL) and TEA (0.106 mL, 0.76 mmol). Intermediate 74A (0.120 g, 0.31 mmol) was added and the mixture stirred at RT for 5 min. and then sodium triacetoxyhydroborate (0.129 g, 0.61 mmol) was added. The mixture was stirred at RT for 21 h. Aqueous NaHCO3 (8%, 6 mL) was added and the mixture was filtered through a phase separator, dichloromethane (4 mL) was added and the solvent was removed by evaporation. The product was purified by preparative HPLC under basic conditions followed by lyophilisation to give (0.106 g, 71%). 1H NMR (400 MHz, CDCl3) δ 1.01 (s, 3H), 1.57-1.71 (m, 1H), 1.95-2.42 (m, 6H), 2.8-3.09 (m, 2H), 3.3-3.41 (m, 1H), 3.44-3.59 (m, 3H), 3.89 (s, 3H), 4.27-4.38 (m, 1H), 4.59-4.83 (m, 2H), 5-5.22 (m, 2H), 6.44 (d, 1H), 6.96-7.17 (m, 4H), 8.10 (d, 2H), MS (APCI+) m/z 493 [M+H]+, LC Purity: 91%.

Workup

  1. stirringThe mixture was stirred at RT for 21 h
  2. filtrationthe mixture was filtered through a phase separator, dichloromethane (4 mL)
  3. additionwas added
  4. customthe solvent was removed by evaporation
  5. customThe product was purified by preparative HPLC under basic conditions
  6. customto give (0.106 g, 71%)

Sources & evidence

ORD record
ord-331be193dcca4aacadbd7c32a3676c5e
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

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