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

HRID 1035257Notes

Reaction equation

HRID 1035257 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:13][C:12]([C:14]([N:16]3[CH2:19][CH:18]([O:20][C:21]4[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=4)[CH2:17]3)=[O:15])=[N:11][N:10]=2)=[CH:5][CH:4]=1.Cl.[CH3:30][C:31]1([CH2:36][OH:37])[CH2:35][CH2:34][NH:33][CH2:32]1.[Na].C([O-])(O)=O.[Na+]>ClCCl>[OH:37][CH2:36][C:31]1([CH3:30])[CH2:35][CH2:34][N:33]([CH2:25][C:24]2[CH:23]=[CH:22][C:21]([O:20][CH:18]3[CH2:19][N:16]([C:14]([C:12]4[O:13][C:9]([C:6]5[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=5)=[N:10][N:11]=4)=[O:15])[CH2:17]3)=[CH:28][CH:27]=2)[CH2:32]1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 580430894-(1-(5-(4-Methoxyphenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehydeHCID 66653455(3-Methylpyrrolidin-3-yl)methanol hydrochloride2×

Product 1

HCID 56599060(3-(4-((3-(Hydroxymethyl)-3-methylpyrrolidin-1-yl)methyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Intermediate 55A (0.165 g, 0.43 mmol), intermediate 84A (3-methylpyrrolidin-3-yl)methanol hydrochloride (0.099 g, 0.65 mmol) and TEA (0.241 mL, 1.74 mmol) were mixed in dichloromethane (4 mL). The mixture was stirred at RT for 30 min and then sodium triacetoxyhydroborate (0.184 g, 0.87 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 than re-purified at pH3 to give 21 mg (10%). 1H NMR (600 MHz, DMSO) δ 1.01 (s, 3H), 1.31-1.39 (m, 1H), 1.57-1.65 (m, 1H), 2.07 (d, 1H), 2.43-2.49 (m, 2H), 3.13-3.25 (m, 3H), 3.46-3.53 (m, 2H), 3.88 (s, 3H), 4.06-4.14 (m, 1H), 4.51-4.67 (m, 2H), 5.05-5.19 (m, 2H), 6.85 (d, 2H), 7.15-7.31 (m, 4H), 8.02 (d, 2H), LC purity: 93%.

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. customthan re-purified at pH3
  6. customto give 21 mg (10%)

Sources & evidence

ORD record
ord-369d794af14b4cec9a3ac4679477144b
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

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