Triethylamine → Isoquinoline-1-carboxylic acid [2-((S)-2-imidazol-1-yl-1-pyridin-3-yl-ethoxy)-5-oxo-5,6,7,8-tetrahydro-naphthalen-1-yl]-amide

HRID 496430Notes

Reaction equation

HRID 496430 reaction equation
[NH2:1][C:2]1[C:11]([O:12][C@@H:13](C2C=CC=CC=2)[CH2:14][N:15]2[CH:19]=[CH:18][N:17]=[CH:16]2)=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][CH2:6][C:7]2=[O:26].[C:27]1([C:37]([OH:39])=O)[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:30]=[CH:29][N:28]=1.CN(C(ON1N=N[C:50]2[CH:51]=[CH:52][CH:53]=[N:54][C:49]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>C(Cl)Cl>[N:15]1([CH2:14][C@H:13]([C:52]2[CH:53]=[N:54][CH:49]=[CH:50][CH:51]=2)[O:12][C:11]2[CH:10]=[CH:9][C:8]3[C:7](=[O:26])[CH2:6][CH2:5][CH2:4][C:3]=3[C:2]=2[NH:1][C:37]([C:27]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:30]=[CH:29][N:28]=2)=[O:39])[CH:19]=[CH:18][N:17]=[CH:16]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 68092Isoquinoline-1-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 600298675-Amino-6-((S)-2-imidazol-1-yl-1-phenyl-ethoxy)-3,4-dihydro-2H-naphthalen-1-one

Product 1

HCID 60029904Isoquinoline-1-carboxylic acid [2-((S)-2-imidazol-1-yl-1-pyridin-3-yl-ethoxy)-5-oxo-5,6,7,8-tetrahydro-naphthalen-1-yl]-amideYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 5-amino-6-((S)-2-imidazol-1-yl-1-phenyl-ethoxy)-3,4-dihydro-2H-naphthalen-1-one (100 mg, 0.287 mmol), 1-isoquinoline carboxylic acid (60 mg, 0.344 mmol), and HATU (131 mg, 0.344 mmol) was added CH2Cl2 (3 mL) and Et3N (48 μL, 0.344 mmol). The reaction was stirred at RT for 5 h. The mixture was diluted with CH2Cl2 and washed with H2O, saturated aqueous NaHCO3 and brine, dried over Na2SO4, and concentrated to give a foam/oil. Purification by chromatography (SiO2, 5-8% MeOH/CH2Cl2) afforded the title compound as a foam (114 mg, 0.226 mmol, 79%). The structure was confirmed by NMR and mass spectrometry. MS m/z 504 (M++H).

Workup

  1. washwashed with H2O, saturated aqueous NaHCO3 and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customto give a foam/oil
  5. customPurification by chromatography (SiO2, 5-8% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ea913423abb44ab2a9d6650e2c72d9e8
Source dataset
uspto-grants-2005_09
Patent number
US06943183B2

Reaction notes

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