1,2,3,4-Tetrahydroisoquinoline → HCID 883945, compound

HRID 2416400Notes

Reaction equation

HRID 2416400 reaction equation
FC(F)(F)C([N:5]1[CH2:13][CH2:12][CH:8]([C:9](O)=[O:10])[CH2:7][CH2:6]1)=O.[CH2:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19][CH2:18][NH:17]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.C([O-])([O-])=O.[K+].[K+]>ClCCl.CO>[CH2:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19][CH2:18][N:17]1[C:9]([CH:8]1[CH2:12][CH2:13][NH:5][CH2:6][CH2:7]1)=[O:10]

Participants

9

Reactant 6

HCID 70461,2,3,4-TetrahydroisoquinolineHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 45521381-(Trifluoroacetyl)piperidine-4-carboxylic acid

Product 1

HCID 883945HCID 883945, compoundYield 76.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

N-Trifluoroacetyl isonipecotic acid (2.56 g, 11.4 mmol), tetrahydroisoquinoline (1.82 g, 13.7 mmol), EDCI (2.63 g, 13.7 mmol), HOBT (1.85 g, 13.7 mmol) and triethylamine (1.38 g, 13.7 mmol) were stirred in dry dichloromethane (30 mL) at 25° C. for 6 h. The reaction was quenched with water and the aqueous phase was extracted with dichloromethane. The combined organic phase was dried over MgSO4 and purified by column chromatography (40/60 EtOAc/hexanes). The solid obtained was stirred with excess K2CO3 in MeOH at 25° C. overnight (16 h). After evaporation of MeOH, the residue was partitioned between dichloromethane and basic water. Evaporation of the organic phase gave pure product as a colorless solid (2.12 g, 76% for two steps). 1H NMR (CDCl3) (mixture of two rotamers) δ 7.23-7.16 (m, 4H), 4.73 (s, 1H), 4.67 (s, 1H), 3.83 (t, J=5.9 Hz, 1H), 3.74 (t, J=5.8 Hz, 1H), 3.21-3.16 (m, 2H), 2.92 (t, J=5.7 Hz, 1H), 2.85 (t, J=5.7 Hz, 1H), 2.76-2.67 (m, 3H), 2.29 (s, 1H), 1.80-1.73 (m, 4H); 13C NMR (CD3OD-CDCl3) δ 6 175.5, 175.3, 135.8, 135.1, 134.0, 133.8, 129.6, 129.3, 127.9, 127.6, 127.4, 127.3, 127.0, 48.2, 45.8, 45.4, 44.2, 41.4, 40.2, 39.6, 39.5, 30.5, 29.5, 29.4, 29.1; LRMS: m/z (relative intensity), 244 (M+, 37%), 188 (100%), 132 (74%); HRMS: calcd. for C15H19N2O 244.1576, found 244.1574. MP: 75-76° C.

Workup

  1. customThe reaction was quenched with water
  2. extractionthe aqueous phase was extracted with dichloromethane
  3. dry with materialThe combined organic phase was dried over MgSO4
  4. custompurified by column chromatography (40/60 EtOAc/hexanes)
  5. customThe solid obtained
  6. customAfter evaporation of MeOH
  7. customthe residue was partitioned between dichloromethane and basic water
  8. customEvaporation of the organic phase

Sources & evidence

ORD record
ord-635db036e26c4e18b8c538c2a5d41216
Source dataset
uspto-grants-2004_11
Patent number
US06825043B1

Reaction notes

Loading…