Diisopropylethylamine → HCID 178488471, compound

HRID 2102240Notes

Reaction equation

HRID 2102240 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]([CH2:14][C:15]3[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][CH:16]=3)[N:12]=[C:11]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)[CH:10]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.O[N:33]1[C:37]2[N:38]=CC=CC=2[N:35]=[N:34]1.C([N:45](C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC.NC1NN=NN=1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>C(Cl)Cl.CN(C=O)C.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]([CH2:14][C:15]3[CH:23]=[CH:22][C:18]([C:19]([NH:45][C:37]4[NH:38][N:35]=[N:34][N:33]=4)=[O:20])=[CH:17][CH:16]=3)[N:12]=[C:11]([C:24]3[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=3)[CH:10]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

9

Reactant 6

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733179PyBroPHCID 67337219HCID 67337219, compoundHCID 178509299HCID 178509299, compound

Product 1

HCID 178488471HCID 178488471, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a solution of the intermediate from step A (100 mg, 0.22 mmol) in 1:1 DMF/DCM (0.54 mL) was added 1-hydroxy-7-azabenzo-triazole (35 mg, 0.264 mmol), NAN-diisopropylethyl amine (92 μL, 0.53 mmol) amino tetrazole (56 mg, 0.66 mmol) and 1-(3-(Dimethylamino)propyl-3-ethyl carbodiimide hydrochloride (51 mg, 0.26 mmol). The reaction was left stirring at room temperature for 18 hours. The reaction was checked by LC-MS and was found to have not gone to completion. An additional equivalent of amino tetrazole was added followed by Bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (51 mg, 0.11 mmol). The reaction was complete in 3 hours. It was diluted with DCM (10 mL) and washed with 1N HCl, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by reverse phase HPLC (Gilson) to give the title compound. 1H NMR (DMSO, 500 MB): δ 8.04(d, J=8.2 Hz, 2H), 7.8(d, J=8.6 Hz, 2H), 7.7(s, 1H), 7.56(d, J=1.8 Hz, 2H), 7.23(d, J=8.2 Hz, 1H), 7.07(s, 1H), 7.01(d, J=9.0 Hz, 2H), 5.56(s, 2H), 3.79(s, 3H). LC-MS: 3.8 min; (M+H)=520.1.

Workup

  1. waitThe reaction was left
  2. waitThe reaction was complete in 3 hours
  3. washwashed with 1N HCl
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by reverse phase HPLC (Gilson)

Sources & evidence

ORD record
ord-35bfe02e586146b58db44d7d43269360
Source dataset
uspto-grants-2009_08
Patent number
US07572922B2

Reaction notes

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