Triethylamine → HCID 9983548, compound

HRID 1294739Notes

Reaction equation

HRID 1294739 reaction equation
[CH:1]1([NH:7][C:8]2[CH:9]=[C:10]([C@@H:14]([N:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)[C:15]3[CH:27]=[CH:26][C:18]([C:19]([N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])=[O:20])=[CH:17][CH:16]=3)[CH:11]=[CH:12][CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.Br[CH2:42][CH:43]1[CH2:45][CH2:44]1>C(#N)C>[CH:1]1([NH:7][C:8]2[CH:9]=[C:10]([C@@H:14]([N:28]3[CH2:33][CH2:32][N:31]([CH2:42][CH:43]4[CH2:45][CH2:44]4)[CH2:30][CH2:29]3)[C:15]3[CH:27]=[CH:26][C:18]([C:19]([N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])=[O:20])=[CH:17][CH:16]=3)[CH:11]=[CH:12][CH:13]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 81503BromomethylcyclopropaneHCID 10049347HCID 10049347, compound

Product 1

HCID 9983548HCID 9983548, compoundYield 81,341%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of COMPOUND 27 (250 mg; 0.56 mmol) in acetonitrile (8 mL) was added triethylamine (92.7 μL; 0.67 mmol). The solution was cooled to 0° C. than bromomethylcyclopropane (53.5 μL; 0.56 mmol) was added. Reaction mixture was stirred overnight then was concentrated under reduced pressure. The residue was dissolved in dichloromethane and washed with water. The organic layer was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. Column chromatography eluting with 5% methanol in dichloromethane gave COMPOUND 72 (229 g; 82% yield). Purity (HPLC-215 nm): >99%; Optical purity (Chiral HPLC-215 nm): >99%. 1H NMR (400 MHz, CD3OD) δ 0.34-0.40 (m, 2H), 0.65-0.71 (m, 2H), 0.99-1.04 (m, 3H), 1.14 (t, J=6.83 Hz, 3H), 1.30-1.35 (m, 6H), 1.61-1.64 (m, 1H), 1.75-1.78 (m, 2H), 1.85-1.90 (m, 2H), 2.46-2.54 (br s, 1H), 2.95-3.03 (br s, 6H), 3.10-3.18 (br s, 2H), 3.37-3.44 (br s, 5H), 3.54-3.60 (br s, 2H), 7.27-2.31 (m, 3H), 7.50-7.53 (m, 3H), 7.64-7.68 (m, 2H). Found: C, 59.91; H, 8.10; N, 10.28. C32H46N4O×3.2HCl×1.1H2O has C, 60.13; H, 8.10; N, 8.76%. [α]D16=+12.4 deg [c 0.51, MeOH].

Workup

  1. additionwas added
  2. customReaction mixture
  3. concentrationthen was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in dichloromethane
  5. washwashed with water
  6. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. washColumn chromatography eluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-bbca0e6b8df74a76a2330bf42dd17c12
Source dataset
uspto-grants-2007_07
Patent number
US07241764B2

Reaction notes

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