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

HRID 1035258Notes

Reaction equation

HRID 1035258 reaction equation
[C:1]1([C:7]2[O:11][C:10]([C:12]([N:14]3[CH2:17][CH:16]([O:18][C:19]4[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=4)[CH2:15]3)=[O:13])=[N:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH3:28][C:29]1([CH2:34][OH:35])[CH2:33][CH2:32][NH:31][CH2:30]1.[Na].C([O-])(O)=O.[Na+]>ClCCl>[OH:35][CH2:34][C:29]1([CH3:28])[CH2:33][CH2:32][N:31]([CH2:23][C:22]2[CH:21]=[CH:20][C:19]([O:18][CH:16]3[CH2:15][N:14]([C:12]([C:10]4[O:11][C:7]([C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)=[N:8][N:9]=4)=[O:13])[CH2:17]3)=[CH:26][CH:25]=2)[CH2:30]1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 58043115HCID 58043115, compoundHCID 66653455(3-Methylpyrrolidin-3-yl)methanol hydrochloride

Product 1

HCID 56599063(3-(4-((3-(Hydroxymethyl)-3-methylpyrrolidin-1-yl)methyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Intermediate 71A (0.15 g, 0.43 mmol), intermediate 84A (0.098 g, 0.64 mmol) and TEA (0.238 mL, 1.72 mmol) were mixed in dichloromethane (4 mL). The mixture was stirred at RT for 30 min and then sodium triacetoxyhydroborate (0.182 g, 0.86 mmol) was added and the mixture was stirred at RT overnight. Aqueous NaHCO3 (sat., 4 mL) and dichloromethane (4 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 21 mg (11%). 1H NMR (600 MHz, DMSO) δ 1.00 (s, 3H), 1.3-1.39 (m, 1H), 1.57-1.64 (m, 1H), 2.05 (d, 1H), 2.41-2.48 (m, 2H), 3.14-3.24 (m, 2H), 3.43-3.51 (m, 2H), 4.07-4.14 (m, 1H), 4.54-4.73 (m, 3H), 5.07-5.19 (m, 2H), 6.85 (d, 2H), 7.25 (d, 2H), 7.63-7.73 (m, 3H), 8.09 (d, 2H), LC purity: 94%.

Workup

  1. stirringthe mixture was stirred at RT overnight
  2. filtrationthe mixture was filtered through a phase separator
  3. customthe solvent was removed by evaporation
  4. customThe product was purified by preparative reverse-phase HPLC at pH 10
  5. customto give 21 mg (11%)

Sources & evidence

ORD record
ord-f7ba6f0e89264227ba39c206ace23749
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

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