Hydrochloric Acid → (R)-Pyrrolidin-2-yl((R)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-yl)methanone

HRID 445357

Reaction equation

HRID 445357 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[C:13]([OH:15])=O)=O)(C)(C)C.[F:16][C:17]([F:35])([F:34])[C:18]1[CH:23]=[CH:22][C:21]([C@@H:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:27][CH2:26][NH:25]2)=[CH:20][CH:19]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl>CN(C=O)C.O1CCOCC1.O>[NH:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[C:13]([N:25]1[CH2:26][CH2:27][C:28]2[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@H:24]1[C:21]1[CH:22]=[CH:23][C:18]([C:17]([F:16])([F:35])[F:34])=[CH:19][CH:20]=1)=[O:15]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 688022(2R)-1-[(tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 28293305(R)-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 59536406(R)-Pyrrolidin-2-yl((R)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-yl)methanone

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a stirred mixture of (R)-1-(tert-butoxy-carbonyl)pyrrolidine-2-carboxylic acid (0.078 g, 0.36 mmol), (R)-1-(4-(trifluoro-methyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (0.100 g, 0.36 mmol) and DIEA (0.047 g, 0.36 mmol) in DMF (2 mL) was added HATU (0.14 g, 0.36 mmol). The reaction mixture was continued to stir overnight at RT, hydrolyzed with H2O, extracted with DCM (3×), dried over Na2SO4, concentrated and purified by ISCO (20% EtOAc/hexanes) to give the white solid which was dissolved in p-dioxane (2 mL) and added 1 mL of 4M HCl in p-dioxane. The mixture was continued to stir at RT overnight, concentrated, taken up in H2O, and neutralized by saturated aqueous NaHCO3, and filtered the light yellow solid which was dried by air. MS (ESI, positive ion) m/z: 375 (M+1).

Workup

  1. extractionextracted with DCM (3×)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. custompurified by ISCO (20% EtOAc/hexanes)
  5. customto give the white solid which
  6. concentrationconcentrated
  7. filtrationfiltered the light yellow solid which
  8. customwas dried by air

Sources & evidence

ORD record
ord-9a93e900122a4fc9b1bab144aa9bc64f
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Linked notes

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