Diisopropylcarbodiimide → (R)-(1-Methyl-4H-pyrazol-3-yl)(1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone

HRID 445302

Reaction equation

HRID 445302 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12][CH2:11][NH:10]2)=[CH:5][CH:4]=1.[CH3:21][N:22]1[CH:26]=[CH:25][C:24]([C:27](O)=[O:28])=[N:23]1.O.ON1C2C=CC=CC=2N=N1.C(N=C=NC(C)C)(C)C>CN(C=O)C.CO>[CH3:21][N:22]1[CH2:26][CH2:25][C:24]([C:27]([N:10]2[CH2:11][CH2:12][C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[C@H:9]2[C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:19])[F:20])=[CH:8][CH:7]=2)=[O:28])=[N:23]1

Participants

7

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 5731761-methyl-1H-pyrazole-3-carboxylic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 28293305(R)-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 68499689(R)-(1-Methyl-4H-pyrazol-3-yl)(1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of (R)-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (58 mg, 0.21 mmol, example 30, step 1) in DMF (1 mL) was added 1-methyl-1H-pyrazole-3-carboxylic acid (Fluorochem, 34 mg, 0.27 mmol), 1-hydroxybenzo-triazole hydrate (42 mg, 0.27 mmol), and N-((isopropylimino)methylene)propan-2-amine (66 μL, 0.42 mmol). The resulting mixture was then stirred at RT for 16 h. Then, the mixture was filtered and the filtrate was purified by preparative HPLC to give the target compound. The product was dissolved in MeOH and passed through PL-HCO3 MP resin and the resin was washed with MeOH (2×0.3 mL). The combined filtrates were concentrated and dried under vacuum to give the title compound as a light-yellow solid. MS (ESI, positive ion) m/z: 386 (M+H).

Workup

  1. filtrationThen, the mixture was filtered
  2. customthe filtrate was purified by preparative HPLC
  3. customto give the target compound
  4. washthe resin was washed with MeOH (2×0.3 mL)
  5. concentrationThe combined filtrates were concentrated
  6. customdried under vacuum

Sources & evidence

ORD record
ord-f558038625ab4c0e95c776ae20159a66
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Linked notes

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