Tetrahydrofuran → HCID 707154, compound

HRID 2274863Notes

Reaction equation

HRID 2274863 reaction equation
[C:1]1([NH2:12])[C:6](F)=[C:5](F)[C:4](F)=[C:3](N)C=1F.Cl.Cl.C([N:17]([CH2:20][CH3:21])CC)C.[CH3:22][C:23]([N:31]=[C:32]=[O:33])([CH3:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[CH2:34]1[CH2:38]OC[CH2:35]1>>[N:12]12[CH2:3][CH2:4][CH:5]([CH2:6][CH2:1]1)[C@H:20]([NH:17][C:32]([NH:31][C:23]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:34]([CH3:38])=[CH2:35])[CH:25]=1)([CH3:22])[CH3:30])=[O:33])[CH2:21]2

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 27694301-Methyl-1-phenyl-ethylisocyanate

Product 1

HCID 707154HCID 707154, compoundYield 47%

Procedure

To a suspension of (S)-(−)-3-aminoquinculidine dihydrochloride (120 mg, 0.603 mmol) and triethylamine (168 uL, 1.21 mmol) in THF (2 mL) at room temperature was added 3-isopropenyl-, -dimethylbenzyl-isocyanate (121 mg, 0.601 mmol). The reaction mixture was stirred for 18 hr and then washed with saturated aqueous NaHCO3. The organic phase was dried over Na2SO4 and concentrated. The crude material was purified on a combiflash (SiO2 cartridge, CHCl3 and 2N NH3 in MeOH) to afford the title compound (29 mg, 47%) as an off-white solid. 1H NMR (400 MHz, CD3OD) δ 7.51 (dt, J=2.5, 1.2 Hz, 1H), 7.41-7.14 (m, 3H), 5.32 (dd, J=1.6, 0.8 Hz, 1H), 5.06 (s, 1H), 3.74-3.60 (m, 1H), 3.31-3.29 (m, 2H), 3.19 (ddd, J=13.7, 9.5, 1.6 Hz, 1H), 2.88-2.50 (m, 4H), 2.37 (ddd, J=14.0, 4.9, 2.2 Hz, 1H), 2.14 (ddd, J=2.3, 1.8, 1.0 Hz, 3H), 1.81-1.63 (m, 4H), 1.62 (d, J=6.2 Hz, 6H), 1.55-1.38 (m, 1H) ppm. 13C NMR (100 MHz, CD3OD) δ 158.4, 148.4, 144.0, 141.3, 128.0, 124.1, 123.3, 121.9, 111.4, 55.7, 54.7, 46.7, 46.4, 46.0, 29.6, 29.4, 28.4, 26.1, 25.1, 21.0, 19.4 ppm. Purity: >96% UPLCMS (210 nm); retention time 0.81 min; (M+1) 329.5.

Workup

  1. additionwas added 3-isopropenyl-
  2. washwashed with saturated aqueous NaHCO3
  3. dry with materialThe organic phase was dried over 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-652b8b835614481a9e06798b7574c802
Source dataset
uspto-grants-2015_09
Patent number
US09126993B2

Reaction notes

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