Triethylamine → HCID 54095263, compound

HRID 1683936Notes

Reaction equation

HRID 1683936 reaction equation
CC1[N:3]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[NH:13][CH:12]=[C:11]3[CH2:17][C@@H:18]2[CH2:22][C@@H:21]([O:23][CH3:24])[CH2:20][N:19]2[CH3:25])C(C)=CC=1.Cl.NO.C(N(CC)CC)C>CC(O)C>[NH2:3][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[CH2:17][C@@H:18]1[CH2:22][C@@H:21]([O:23][CH3:24])[CH2:20][N:19]1[CH3:25]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 54048218HCID 54048218, compound

Product 1

HCID 54095263HCID 54095263, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 5-(2,5-dimethyl-1H-pyrrolyl)-3-[(2R,4R)-N-methyl-4-methoxypyrrolidin-2-ylmethyl]-1H-indole (2.20 g, 6.52 mmol), hydroxylamine hydrochloride (7.25 g, 104 mmol, 16 eq), and triethylamine (7.28 mL, 52.2 mmol, 8 eq) in 2-propanol (22 mL) was heated at reflux under nitrogen for 8 hours. The resulting reaction solution was evaporated under reduced pressure, and the residue was partitioned between ethyl acetate (50 mL) and a saturated solution of sodium hydrogen carbonate (50 mL). The ethyl acetate layer was removed, and the aqueous layer was extracted with methylene chloride (3×50 mL). All organic extracts were combined, dried (MgSO4), and evaporated under reduced pressure to afford the title compound (1.68 g, 100%) as an off-white amorphous solid: Rf =0.4 in 9:1:0.1 [methylene chloride/methanol/ammonium hydroxide]; 1H NMR (CD3OD) δ7.14 (d, J=8.5 Hz, 1H), 6.99 (s, 1H), 6.94 (br s, 1H), 6.68 (br d, J=8.5 Hz, 1H), 4.90 (s, 3-NH), 3.86-3.77 (m, 1H), 3.24 (s, 3H), 3.24-3.13 (m, 2H), 2.93-2.80 (m, 1H), 2.69 (dd, J=13.7 and 9.7 Hz, 1H), 2.51 (s, 3H), 2.40-2.18 (m, 2H), 1.73-1.63 (m, 1H); 13C NMR (CD3OD) δ139.7, 133.4, 129.3, 124.4, 114.4, 112.8, 111.2, 105.5, 79.3, 68.3, 66.1, 56.7, 40.7, 39.5, 30.1.

Workup

  1. temperaturewas heated
  2. temperatureat reflux under nitrogen for 8 hours
  3. customThe resulting reaction solution
  4. customwas evaporated under reduced pressure
  5. customthe residue was partitioned between ethyl acetate (50 mL)
  6. customThe ethyl acetate layer was removed
  7. extractionthe aqueous layer was extracted with methylene chloride (3×50 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-717dda5d6afe414b985f94d2b44ba4bc
Source dataset
uspto-grants-1997_06
Patent number
US05639752

Reaction notes

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