Triethylamine → N-[1-(3,4-dichlorobenzyl)-pyrrolidin-3-(RS)-ylmethyl]-2-(9H-1,3,4,9-tetraazafluoren-2-ylsulfanyl)acetamide

HRID 1276377Notes

Reaction equation

HRID 1276377 reaction equation
[N:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[N:4]=[N:3][C:2]=1[S:14][CH2:15][C:16]([OH:18])=O.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[NH2:49][CH2:50][CH:51]1[CH2:55][CH2:54][N:53]([CH2:56][C:57]2[CH:62]=[CH:61][C:60]([Cl:63])=[C:59]([Cl:64])[CH:58]=2)[CH2:52]1>C(Cl)(Cl)Cl.CN(C)C=O>[Cl:64][C:59]1[CH:58]=[C:57]([CH:62]=[CH:61][C:60]=1[Cl:63])[CH2:56][N:53]1[CH2:54][CH2:55][CH:51]([CH2:50][NH:49][C:16](=[O:18])[CH2:15][S:14][C:2]2[N:3]=[N:4][C:5]3[C:6]4[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=4)[NH:12][C:13]=3[N:1]=2)[CH2:52]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 5404907(2H-[1,2,4]Triazino[5,6-b]indol-3-ylsulfanyl)-acetic acidHCID 221153103-Aminomethyl-1-(3,4-dichlorobenzyl)pyrrolidine

Product 1

HCID 22115346N-[1-(3,4-dichlorobenzyl)-pyrrolidin-3-(RS)-ylmethyl]-2-(9H-1,3,4,9-tetraazafluoren-2-ylsulfanyl)acetamide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

Solid (9H-1,3,4,9-tetraazafluoren-2-ylsulfanyl)acetic acid (390 mg, 1.5 mmol, 1.2 equiv.) was added to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (360 mg, 1.9 mmol, 1.5 equiv.), 1-hydroxybenzotriazole hydrate (260 mg, 1.9 mmol, 1.5 equiv.) and triethylamine (0.65 mL, 4.6 mmol, 3.7 equiv.) in chloroform (10 mL). 3-(RS)-Aminomethyl-1-(3,4-dichlorobenzyl)pyrrolidine (320 mg, 1.2 mmol) was added and the suspension was made homogeneous upon addition of dimethylformamide (5 mL). The brown solution was stirred for 14 h, then concentrated in vacuo. The residue was diluted with ethyl acetate and washed with 1 M sodium hydroxide. The organic phase was concentrated to dryness and the residue purified by chromatography (5→10% methanol in CHCl3) to provide N-[1-(3,4-dichlorobenzyl)-pyrrolidin-3-(RS)-ylmethyl]-2-(9H-1,3,4,9-tetraazafluoren-2-ylsulfanyl)acetamide as a pale yellow solid. The solid was dissolved into 4 M HCl in dioxane (1 mL) and the mixture concentrated under vacuum to afford pure product as its hydrochloride salt (250 mg).

Workup

  1. concentrationconcentrated in vacuo
  2. additionThe residue was diluted with ethyl acetate
  3. washwashed with 1 M sodium hydroxide
  4. concentrationThe organic phase was concentrated to dryness
  5. customthe residue purified by chromatography (5→10% methanol in CHCl3)

Sources & evidence

ORD record
ord-ca5e9b4b33f146f59a7f1d45993a74e8
Source dataset
uspto-grants-2000_12
Patent number
US06166015

Reaction notes

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