Pyrazole → 2-[2-(4-Cyclobutylpiperazin-1-Yl)-2-Oxoethyl]-6-(1H-Pyrazol-1-Yl)-1,2,3,4-Tetrahydroisoquinoline

HRID 1713102Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][N:7]([CH2:12][C:13]([N:15]1[CH2:20][CH2:19][N:18]([CH:21]3[CH2:24][CH2:23][CH2:22]3)[CH2:17][CH2:16]1)=[O:14])[CH2:6][CH2:5]2.[NH:25]1[CH:29]=[CH:28][CH:27]=[N:26]1.C(=NO)C1C(=CC=CC=1)O.C([O-])([O-])=O.[Cs+].[Cs+]>CC#N>[CH:21]1([N:18]2[CH2:19][CH2:20][N:15]([C:13](=[O:14])[CH2:12][N:7]3[CH2:6][CH2:5][C:4]4[C:9](=[CH:10][CH:11]=[C:2]([N:25]5[CH:29]=[CH:28][CH:27]=[N:26]5)[CH:3]=4)[CH2:8]3)[CH2:16][CH2:17]2)[CH2:24][CH2:23][CH2:22]1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 6-bromo-2-[2-(4-cyclobutylpiperazin-1-yl)-2-oxoethyl]-1,2,3,4-tetrahydroisoquinoline (120 mg, 0.307 mmol), pyrazole (31 mg, 0.46 mmol), Cu2O (4 mg, 0.03 mmol), salicylaldoxime (16 mg, 0.12 mmol) and Cs2CO3 (300 mg, 0.92 mmol) in CH3CN (8 mL) is degassed by argon and heated at 120° C. in a sealed tube overnight. EtOAc (10 mL) is added and the mixture is filtered. The organic layer is washed with brine (10 mL) and dried. Purification of the residue by PTLC gives title compound as a light yellow solid. MS (M+1): 380.2; 1H NMR (δ, CDCl3): 7.88 (d, 1H), 7.70 (d, 1H), 7.47 (d, 1H), 7.41 (dd, 1H), 7.08 (d, 1H), 6.45 (dd, 1H), 3.71 (s, 2H), 3.65 (t, 4H), 3.38 (s, 2H), 2.96 (t, 2H), 2.81 (t, 2H), 2.63-2.72 (m, 1H), 2.28 (q, 4H), 1.64-2.08 (m, 6H).

Workup

customis degassed by argon
additionEtOAc (10 mL) is added
filtrationthe mixture is filtered
washThe organic layer is washed with brine (10 mL)
customdried
customPurification of the residue by PTLC

Sources & evidence

ORD record: ord-3fbd91f6ea6d45cb85018dcf3abc12ce
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07795262B2

Reaction notes

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