Triethylamine → HCID 44218744, compound

HRID 1469352Notes

Reaction equation

HRID 1469352 reaction equation
Cl.[C:2]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:7]=[CH:6][C:5]([O:8][CH:9]2[CH2:12][NH:11][CH2:10]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH:26]1[CH:31]=[N:30][CH:29]=[C:28]([N:32]=[C:33]=[O:34])[CH:27]=1>ClCCl>[N:30]1[CH:31]=[CH:26][CH:27]=[C:28]([NH:32][C:33]([N:11]2[CH2:12][CH:9]([O:8][C:5]3[CH:6]=[CH:7][C:2]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)=[CH:3][CH:4]=3)[CH2:10]2)=[O:34])[CH:29]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27604933-IsocyanatopyridineHCID 66710170HCID 66710170, compound

Product 1

HCID 44218744HCID 44218744, compoundYield 36.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

3-(Biphenyl-4-yloxy)azetidine hydrochloride (3 g, 11.47 mmol) was suspended in dichloromethane (45 mL) under a nitrogen atmosphere, treated with triethylamine (4.0 mL, 28.68 mmol) and stirred for 10 minutes at room temperature. The mixture was cooled to 0° C. and treated portionwise with pyridine-3-isocyanate (1.15 g, 9.56 mmol). Stirred at 0° C. for 10 minutes, then at rt for 16 hours. The solution was diluted with further dichloromethane (200 mL), washed with H2O (2×100 mL), followed by brine (50 mL), dried (over MgSO4), and solvent evaporated in vacuo to yield an off-white solid. The solid was triturated with diethyl ether, then stirred for 3 days with MP-isocyanate resin in a dichloromethane/methanol/acetonitrile mixture. The mixture was filtered and reduced to dryness in vacuo. The resulting solid was triturated successively with diethyl ether, then acetonitrile and filtered to give the urea (1.2 g, 36%) as a white solid; Rf 0.10 (5% MeOH-DCM); LCMS retention time 2.08 minutes, m/z 346.2 [M+H]+; 1H nmr (400 MHz; DMSO-d6) δ 8.97 (s, 1H), 8.75 (d, 1H, J=2.3 Hz), 8.21 (d, 1H, J=4.7 Hz), 8.05-8.01 (m, 1H), 7.65-7.60 (m, 4H), 7.44 (t, 2H, J=7.9 Hz), 7.39 (dd, 1H, J=8.3 and 4.7 Hz), 7.32 (t, 1H, J=7.3 Hz), 6.96 (d, 2H, J=8.8 Hz), 5.14-5.08 (m, 1H), 4.49 (dd, 2H, J=9.5 and 6.5 Hz) and 3.97 (dd, 2H, J=9.5 and 3.8 Hz); 13C nmr (100 MHz; DMSO-d6) 156.2 (C), 155.9 (C), 141.4 (CH), 139.6 (C), 138.9 (CH), 137.3 (C), 133.4 (C), 128.9 (CH), 128.1 (CH), 126.9 (CH), 126.8 (CH), 126.3 (CH), 123.9 (CH), 115.1 (CH), 65.6 (CH) and 56.4 (CH2).

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. stirringStirred at 0° C. for 10 minutes
  3. waitat rt for 16 hours
  4. washwashed with H2O (2×100 mL)
  5. dry with materialdried (over MgSO4), and solvent
  6. customevaporated in vacuo
  7. customto yield an off-white solid
  8. customThe solid was triturated with diethyl ether
  9. stirringstirred for 3 days with MP-isocyanate resin in a dichloromethane/methanol/acetonitrile mixture
  10. filtrationThe mixture was filtered
  11. customThe resulting solid was triturated successively with diethyl ether
  12. filtrationacetonitrile and filtered

Sources & evidence

ORD record
ord-af9672fa194d47a4a68f9189f1906972
Source dataset
uspto-grants-2015_04
Patent number
US09006269B2

Reaction notes

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