Diisopropylethylamine → HCID 178488473, compound

HRID 2102237Notes

Reaction equation

HRID 2102237 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[N:11]([CH2:22][C:23]3[CH:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][CH:24]=3)[N: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](CC)C(C)C)(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[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[N:11]([CH2:22][C:23]3[CH:31]=[CH:30][C:26]([C:27]([NH:45][C:37]4[NH:38][N:35]=[N:34][N:33]=4)=[O:28])=[CH:25][CH:24]=3)[N: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 67335518HCID 67335518, compoundHCID 178509299HCID 178509299, compound

Product 1

HCID 178488473HCID 178488473, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a solution of the intermediate from step D (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), N,N-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 MHz): δ 8.04(d, J=8.5 Hz, 2H), 7.89(d, J=2.1 Hz, 2H), 7.56(t, J=1.9 Hz, 1H), 7.41(d, J=8.7 Hz, 2H), 7.21(d, J=8.4 Hz, 2H), 7.14(s, 1H), 7.05(d, J=8.7 Hz, 2H), 5.53(s, 2H), 3.79(s, 3H). LC-MS: 2.53 min; (M+H)=520.2.

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-5f90e1a26faf478ea1cdf567f2bd677b
Source dataset
uspto-grants-2009_08
Patent number
US07572922B2

Reaction notes

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