1,2-Dichloroethane → (6-Bromo-pyrazolo[1,5-a]pyrimidin-2-yl)-(1-methyl-3,4-dihydro-1H-isoquinolin-2-yl)-methanone

HRID 1015110Notes

Reaction equation

HRID 1015110 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([OH:13])=O)[CH:10]=2)[CH:7]=1.[CH3:14][CH:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18][CH2:17][NH:16]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([N:16]3[CH2:17][CH2:18][C:19]4[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:15]3[CH3:14])=[O:13])[CH:10]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 922141-Methyl-1,2,3,4-tetrahydroisoquinolineHCID 7719386-Bromopyrazolo[1,5-a]pyrimidine-2-carboxylic acid

Product 1

HCID 24810370(6-Bromo-pyrazolo[1,5-a]pyrimidin-2-yl)-(1-methyl-3,4-dihydro-1H-isoquinolin-2-yl)-methanoneYield 58.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 28 mg (0.12 mmol) of 6-Bromo-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid, 19 mg (0.13 mmol) of 1-methyl-1,2,3,4-tetrahydro-isoquinoline, 23 mg (0.12 mmol) of EDC and 19 mg (0.12 mmol) of HOBt in 2 mL of DMF is stirred at room temperature for 24 h. The mixture is concentrated in vacuo and the solid residue is partitioned between methylene chloride (3 mL) and saturated aqueous sodium hydrocarbonate solution (3 mL). The organic layer is separated, washed with 0.5 N HCl, water and brine and concentrated in vacuo. Purification of the residue by flash column chromatography (chloroform:methanol 99:1) gives 26 mg (58%) of title compound as a crystalline solid.

Workup

  1. concentrationThe mixture is concentrated in vacuo
  2. customthe solid residue is partitioned between methylene chloride (3 mL) and saturated aqueous sodium hydrocarbonate solution (3 mL)
  3. customThe organic layer is separated
  4. washwashed with 0.5 N HCl, water and brine
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by flash column chromatography (chloroform:methanol 99:1)

Sources & evidence

ORD record
ord-2b4d504585784e619b8079746946ba6b
Source dataset
uspto-grants-2011_07
Patent number
US07985753B2

Reaction notes

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