Pyridine → Phenylmethyl 6-[3-(1,1-dimethylethyl)-5-(ethoxycarbonyl)-1H-pyrazol-1-yl]-3,4-dihydro-2(1H)-isoquinolinecarboxylate

HRID 2042084Notes

Reaction equation

HRID 2042084 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16](B(O)O)[CH:17]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[C:30]([C:34]1[CH:38]=[C:37]([C:39]([O:41][CH2:42][CH3:43])=[O:40])[NH:36][N:35]=1)([CH3:33])([CH3:32])[CH3:31]>C(Cl)Cl.O.CC([O-])=O.CC([O-])=O.[Cu+2]>[C:30]([C:34]1[CH:38]=[C:37]([C:39]([O:41][CH2:42][CH3:43])=[O:40])[N:36]([C:16]2[CH:17]=[C:18]3[C:13](=[CH:14][CH:15]=2)[CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[CH2:20][CH2:19]3)[N:35]=1)([CH3:33])([CH3:31])[CH3:32]

Participants

7

Reactant 3

HCID 1049PyridineHCID 2743509Ethyl 3-tert-butyl-1H-pyrazole-5-carboxylateHCID 67252216HCID 67252216, compound

Product 1

HCID 67253043Phenylmethyl 6-[3-(1,1-dimethylethyl)-5-(ethoxycarbonyl)-1H-pyrazol-1-yl]-3,4-dihydro-2(1H)-isoquinolinecarboxylateYield 48.4%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a stirring suspension of 2-(benzyloxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-ylboronic acid (0.640 g, 2.06 mmol, 1.00 eq) and 4 ÅMS (0.64 g) in CH2Cl2 (20 ml) was added pyridine (0.168 ml, 2.06 mmol, 1.00 eq) followed by ethyl 3-t-butyl-1H-pyrazole-5-carboxylate (0.404 g, 2.06 mmol, 1.00 eq) and Cu(OAc)2 (0.374 g, 2.06 mmol, 1.00 eq). The resulting blue-green mixture was stirred at 25° C. After 40 h, the mixture was diluted with H2O and decanted away from the molecular sieves. The layers were separated and the organic phase was washed with H2O (2×). The combined aqueous phases were extracted with CH2Cl2 (1×). The combined organic phases were dried (MgSO4), concentrated in vacuo and purified by flash chromatography (EtOAc/hexanes) to afford benzyl 6-(3-t-butyl-5-(ethoxycarbonyl)-1H-pyrazol-1-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (0.46 g, 48% yield). 1H NMR (400 MHz, DMSO-d6) δ 7.41-7.28 (m, 5H), 7.24-7.20 (m, 3H), 6.96 (s, 1H), 5.15 (s, 2H), 4.67 (brm, 2H), 4.17 (q, 2H, J=7.2 Hz), 3.66 (brs, 2H), 2.86 (t, 2H, J=6.0 Hz), 1.29 (s, 9H), 1.18 (t, 3H, J=7.2 Hz); MS (ESI) m/z: 462.3 (M+H+).

Workup

  1. customdecanted away from the molecular sieves
  2. customThe layers were separated
  3. washthe organic phase was washed with H2O (2×)
  4. extractionThe combined aqueous phases were extracted with CH2Cl2 (1×)
  5. dry with materialThe combined organic phases were dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. custompurified by flash chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-c9b38623198a49d2a4328d4dafa72571
Source dataset
uspto-grants-2013_11
Patent number
US08586565B2

Reaction notes

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