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

HRID 1035261Notes

Reaction equation

HRID 1035261 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([OH:38])[CH2:37][CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.[Na].C([O-])(O)=O.[Na+]>ClCCl>[OH:38][C:31]1([CH3:30])[CH2:37][CH2:36][CH2:35][N:34]([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)[CH2:33][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 666532494-Hydroxy-4-Methyl-Hexahydro-1H-azepine hydrochloride

Product 1

HCID 56599064(3-(4-((4-Hydroxy-4-methylazepan-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 (0.10 g, 0.26 mmol), 4-methylazepan-4-ol hydrochloride (0.057 g, 0.34 mmol, see Helvetica Chimica Acta, 45, 1823-32, (1962)) and TEA (0.146 mL, 1.05 mmol) were mixed in dichloromethane (4 mL). The mixture was stirred at RT for 1 h and then sodium triacetoxyhydroborate (0.112 g, 0.53 mmol) was added and the mixture was stirred at RT overnight. Aqueous NaHCO3 (sat., 3 mL) and dichloromethane (3 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 83 mg (64%). 1H NMR (600 MHz, DMSO) δ 1.11 (s, 3H), 1.35-1.8 (m, 7H), 2.31-2.65 (m, 3H), 3.51 (s, 2H), 3.88 (s, 3H), 4.07-4.12 (m, 1H), 4.51-4.66 (m, 2H), 5.06-5.18 (m, 2H), 6.85 (d, 2H), 7.16-7.3 (m, 4H), 8-8.06 (m, 2H), LC-purity: 92%.

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 83 mg (64%)

Sources & evidence

ORD record
ord-3213c0309da344fe848e26b916364aba
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

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