1-Hydroxybenzotriazole → HCID 90149508, compound

HRID 2202543Notes

Reaction equation

HRID 2202543 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])C(O)=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH2:29]([N:31]=[C:32]=[N:33][CH2:34][CH2:35][CH2:36][N:37]([CH3:39])C)C.[CH:40]1[CH:41]=[CH:42][C:43]2N(O)N=N[C:44]=2[CH:45]=1.[OH:50][CH2:51]C(C1C(OC)=NC2C(C=1)=CC=CC=2)=O.C([O-])(=O)C.[NH4+]>CN(C=O)C.CN(C1C=CN=CC=1)C.C1(C)C(C)=CC=CC=1.CCOC(C)=O.O>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:32]1[NH:33][C:34]([C:35]2[C:36]([O:50][CH3:51])=[N:37][C:39]3[C:43]([CH:44]=2)=[CH:42][CH:41]=[CH:40][CH:45]=3)=[CH:29][N:31]=1)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

11

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 517165Ammonium AcetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7408150HCID 7408150, compoundHCID 44158083HCID 44158083, compound

Product 1

HCID 90149508HCID 90149508, compound

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 7237O-XyleneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (S)-2-(((benzyloxy)carbonyl)amino)-8-(tert-butoxy)-8-oxooctanoic acid (prepared as described in WO2006/061638), N-ethyl-N′-(3-dimethylaminopropyl)-carbo diimide hydrochloride (1.3 eq.) and HOBt (1.3 eq.) were dissolved in anhydrous DMF and stirred for 15 min. The resulting solution was added to a mixture of 2-hydroxy-1-(2-methoxyquinolin-3-yl)ethanone (1 eq.) (prepared as described in J. Med. Chem. 2009, 59, 3453-3456) and DMAP (0.3 eq.) in anhydrous DMF (0.7 M). After stirring at room temperature for 16 h the mixture was partitioned between DCM and water. The organic phase was washed with water and brine and dried over Na2SO4. Concentration under reduced pressure gave an oily crude which was used as such. A solution of the resulting oil and ammonium acetate (20 eq.) in xylene was heated under Dean-Stark conditions for 1.5 h. After cooling to room temperature the mixture was diluted with EtOAc and water. The organic phase was separated and washed with sat. aq. NaHCO3, brine, dried over Na2SO4 and concentrated under reduced pressure to give a crude that was purified by column chromatography (eluent: petroleum ether/EtOAc from 7:3 to 2:3) to give the title compound as a yellow powder. MS (ES+) C32H38N4O5: 559 (M+H)+.

Workup

  1. stirringAfter stirring at room temperature for 16 h the mixture
  2. customwas partitioned between DCM and water
  3. washThe organic phase was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationConcentration under reduced pressure
  6. customgave an oily crude which
  7. customThe organic phase was separated
  8. washwashed with sat. aq. NaHCO3, brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customto give a crude that
  12. customwas purified by column chromatography (eluent: petroleum ether/EtOAc from 7:3 to 2:3)

Sources & evidence

ORD record
ord-a0fefa5bfef147d8829c8956ea96667a
Source dataset
uspto-grants-2016_06
Patent number
US09365541B2

Reaction notes

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