1-Amino-11-azido-3,6,9-trioxaundecane → 1-(2-(2-(2-(2-Azidoethoxy)ethoxy)ethoxy)ethyl)-3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)urea

HRID 45721Notes

Reaction equation

HRID 45721 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:15]=[C:16]([NH:20][C:21](=[O:32])OC2C=CC([N+]([O-])=O)=CC=2)[CH:17]=[CH:18][CH:19]=1.[N:33]([CH2:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][NH2:47])=[N+:34]=[N-:35]>CN(C=O)C>[N:33]([CH2:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][NH:47][C:21]([NH:20][C:16]1[CH:17]=[CH:18][CH:19]=[C:14]([CH:5]2[C:4]3[C:9](=[C:10]([Cl:12])[CH:11]=[C:2]([Cl:1])[CH:3]=3)[CH2:8][N:7]([CH3:13])[CH2:6]2)[CH:15]=1)=[O:32])=[N+:34]=[N-:35]

Participants

4

Reactant 2

HCID 27352801-Amino-11-azido-3,6,9-trioxaundecaneHCID 223868934-Nitrophenyl 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylcarbamate

Product 1

HCID 866993811-(2-(2-(2-(2-Azidoethoxy)ethoxy)ethoxy)ethyl)-3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)urea

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 4-nitrophenyl 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylcarbamate (prepared by the procedure described in example 38) (200 mg, 0.40 mmol, 1.00 equiv, 95%) in DMF (5 mL) was added TEA (170 mg, 1.60 mmol, 4.00 equiv, 95%) and 2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethanamine (90 mg, 0.39 mmol, 1.00 equiv, 95%) and the resulting solution was stirred for 2 h. The mixture was then concentrated under vacuum, diluted with 10 mL of water and then extracted with 3×30 mL of ethyl acetate. The organic layers were combined, washed with 3×30 mL of brine, dried over anhydrous sodium sulfate and then evaporated. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5˜1:1). This resulted in 160 mg (72%) of 1-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl)-3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)urea as pale-yellow oil.

Workup

  1. concentrationThe mixture was then concentrated under vacuum
  2. additiondiluted with 10 mL of water
  3. extractionextracted with 3×30 mL of ethyl acetate
  4. washwashed with 3×30 mL of brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated
  7. customThis resulted in 160 mg (72%) of 1-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl)-3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)urea as pale-yellow oil

Sources & evidence

ORD record
ord-086daa88229741c2949c34a628b6a135
Source dataset
uspto-grants-2013_09
Patent number
US08541448B2

Reaction notes

Loading…