Hydrochloric Acid → HCID 130312483, compound

HRID 1481863Notes

Reaction equation

HRID 1481863 reaction equation
CC1(C)[O:6][C@H:5]2[CH2:7][CH2:8][CH2:9][C@H:10]([N:11]3[CH2:20][CH2:19][C:18]4[C:13](=[CH:14][C:15]([NH:34][C:35]([C:37]5[N:38]=[C:39]([CH:42]6[CH2:44][CH2:43]6)[O:40][CH:41]=5)=[O:36])=[C:16]([N:21]5[CH2:26][CH2:25][N:24]([C:27]6[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=6[CH3:33])[CH2:23][CH2:22]5)[CH:17]=4)[C:12]3=[O:45])[C@H:4]2[O:3]1.Cl>CO.ClCCl>[OH:3][C@H:4]1[C@@H:5]([OH:6])[CH2:7][CH2:8][CH2:9][C@@H:10]1[N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][C:15]([NH:34][C:35]([C:37]3[N:38]=[C:39]([CH:42]4[CH2:43][CH2:44]4)[O:40][CH:41]=3)=[O:36])=[C:16]([N:21]3[CH2:22][CH2:23][N:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[CH3:33])[CH2:25][CH2:26]3)[CH:17]=2)[C:12]1=[O:45]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 130312499HCID 130312499, compound

Product 1

HCID 130312483HCID 130312483, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-cyclopropyl-oxazole-4-carboxylic acid [(S)-2-((3aR,7aS)-2,2-dimethyl-hexahydro-benzo[1,3]dioxol-4-yl)-1-oxo-6-(4-o-tolyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-7-yl]-amide (0.165 g, 0.26 mmol) in anhydrous methanol (2 mL) was added methanolic HCl (5 mL) at 0° C. under N2 atmosphere. The reaction mixture was allowed to stir at room temperature for 1 h. The progress of the reaction was monitored by the TLC. Upon completion of the reaction, the reaction mixture was concentrated in vacuo, residue obtained was diluted with dichloromethane (100 mL); and was washed with 10% NaHCO3 solution, water followed by brine solution and dried over anhydrous Na2SO4. The crude product obtained was purified by the flash column chromatography (230-400 size mesh) by eluting 3.25-3.5% methanol in dichloromethane to afford the title compound. Finally, the title compound 2-cyclopropyl-oxazole-4-carboxylic acid [(S)-2-((2R,3S)-2,3-dihydroxy-cyclohexyl)-1-oxo-6-(4-o-tolyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-7-yl]-amide was purified again by preparative HPLC to afford the pure compound. Yield (0.110 g, 65%, off white solid).

Workup

  1. customUpon completion of the reaction
  2. concentrationthe reaction mixture was concentrated in vacuo, residue
  3. customobtained
  4. washand was washed with 10% NaHCO3 solution, water
  5. dry with materialdried over anhydrous Na2SO4
  6. customThe crude product obtained
  7. customwas purified by the flash column chromatography (230-400 size mesh)
  8. washby eluting 3.25-3.5% methanol in dichloromethane

Sources & evidence

ORD record
ord-8c7f925a1f2e43e089f96f51e4988cb7
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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