1,2,3,4-Tetrahydroisoquinoline → 3-Benzyloxy-5-methyl-4-oxo-2-[(1,2,3,4-tetrahydro-isoquinolin-2-yl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine

HRID 1453858Notes

Reaction equation

HRID 1453858 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:20](O)=[O:21])=[N:11][N:12]2[CH2:17][CH2:16][N:15]([CH3:18])[C:14](=[O:19])[C:13]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:47]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH2:50][CH2:49][NH:48]1>CN(C=O)C>[CH2:1]([O:8][C:9]1[C:10]([C:20]([N:48]2[CH2:49][CH2:50][C:51]3[C:56](=[CH:55][CH:54]=[CH:53][CH:52]=3)[CH2:47]2)=[O:21])=[N:11][N:12]2[CH2:17][CH2:16][N:15]([CH3:18])[C:14](=[O:19])[C:13]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 70461,2,3,4-TetrahydroisoquinolineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 689513253-Benzyloxy-5-methyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylic acid

Product 1

HCID 689539593-Benzyloxy-5-methyl-4-oxo-2-[(1,2,3,4-tetrahydro-isoquinolin-2-yl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-benzyloxy-5-methyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylic acid (60 mg, 0.199 mmol) in DMF (2 mL) under an atmosphere of nitrogen was added HATU (152 mg, 0.398 mmol) and 1,2,3,4-tetrahydroisoquinoline (32 mg, 0.239 mmol). The reaction was stirred at room temperature for 1 hour. Purification by reverse phase chromatography on a C-18 column using a gradient elution of 95-5% H2O (0.1% TFA)/CH3CN (0.1% TFA) and collection and concentration of the appropriate fractions afforded the title product. 1H NMR (400 MHz, CDCl3) δ 7.69-7.58 (m, 1H), 7.53-7.48 (m, 1H), 7.33-7.30 (m, 1H), 7.22-7.10 (m, 4H), 7.08-7.06 (d, 1H), 6.94-6.92 (d, 1H), 5.24-5.22 (d, 2H), 4.81 (s, 1H), 4.60 (s, 1H), 4.39-4.35 (t, 2H), 3.90-3.87 (m, 1H), 3.78-3.75 (t, 2H), 3.64-3.61 (t, 1H), 3.18 (s, 3H), 2.93-2.90 (t, 1H), 2.82-2.79 (t, 1H); ES MS (M+1)=417.

Workup

  1. customPurification by reverse phase chromatography on a C-18 column
  2. washa gradient elution of 95-5% H2O (0.1% TFA)/CH3CN (0.1% TFA) and collection and concentration of the appropriate fractions

Sources & evidence

ORD record
ord-bcbba3702238428090e21d952e6d45c4
Source dataset
uspto-grants-2009_01
Patent number
US07476666B2

Reaction notes

Loading…