Triethylamine → HCID 707151, compound

HRID 2274859Notes

Reaction equation

HRID 2274859 reaction equation
Cl.Cl.[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH2:11])[CH2:4]2.[N:12]([C:15]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([CH3:26])=[CH2:25])[CH:19]=1)([CH3:17])[CH3:16])=[C:13]=[O:14].C(N(CC)CC)C>C1COCC1>[CH2:25]=[C:24]([C:20]1[CH:19]=[C:18]([C:15]([NH:12][C:13]([NH:11][C@@H:5]2[CH:6]3[CH2:9][CH2:10][N:3]([CH2:8][CH2:7]3)[CH2:4]2)=[O:14])([CH3:17])[CH3:16])[CH:23]=[CH:22][CH:21]=1)[CH3:26]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 6041521-(1-Isocyanato-1-methylethyl)-3-(1-methylethenyl)benzeneHCID 12494972(R)-(+)-3-Aminoquinuclidine Dihydrochloride

Product 1

HCID 707151HCID 707151, compoundYield 83.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-quinuclidin-3-amine dihydrochloride (120 mg, 0.603 mmol) and 1-(2-isocyanatopropan-2-yl)-3-(prop-1-en-2-yl)benzene (119 mg, 0.597 mmol) in THF (3 mL) was added triethylamine (168 uL, 1.21 mmol). The reaction mixture was stirred at room temperature for 18 h and then quenched with brine. The mixture was extracted with CHCl3 and the organic layer was dried (Na2SO4) and concentrated. The crude material was purified on a combiflash (SiO2 cartridge, CHCl3 and 2N NH3 in MeOH) to afford the corresponding urea (163 mg, 50%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.62 (t, J=1.6 Hz, 1H), 7.44 (dt, J=1.9, 7.0 Hz, 1H), 7.41-7.33 (m, 2H), 5.35 (br s, 1H), 5.11 (p, J=1.4 Hz, 1H), 4.84 (s, 1H), 4.21 (d, J=7.5 Hz, 1H), 3.70-3.61 (m, 1H), 3.13 (ddd, J=2.3, 9.3, 14.2 Hz, 1H), 2.71-2.54 (m, 3H), 2.30-2.22 (m, 1H), 2.15 (dd, J=0.8, 1.4, 3H), 2.05-1.96 (m, 1H), 1.65 (s, 3H), 1.64 (s, 3H), 1.65-1.60 (m, 1H) 1.54-1.45 (m, 2H), 1.22-1.12 (m, 1H), 0.95-0.80 (m, 1H) ppm. 13C NMR (400 MHz, CDCl3) δ 157.4, 148.5, 143.8, 141.3, 128.4, 124.4, 123.8, 122.2, 112.6, 55.2, 53.4, 46.2, 46.1, 44.5, 30.5, 30.4, 25.0, 22.2, 17.7, 8.9 ppm. Purity: 97.5% UPLCMS (210 nm); retention time 0.83 min; (M+1) 328.

Workup

  1. customquenched with brine
  2. extractionThe mixture was extracted with CHCl3
  3. dry with materialthe organic layer was dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe crude material was purified on a combiflash (SiO2 cartridge, CHCl3 and 2N NH3 in MeOH)

Sources & evidence

ORD record
ord-056e096053984aedbcdaee298c9842cb
Source dataset
uspto-grants-2015_09
Patent number
US09126993B2

Reaction notes

Loading…