Water → 4-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine

HRID 2090281Notes

Reaction equation

HRID 2090281 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[N:5]=[C:4]([NH2:15])[N:3]=1.[Br:16][C:17]1[CH:26]=[C:25]2[C:20]([CH2:21][CH2:22][NH:23][CH2:24]2)=[CH:19][CH:18]=1.CN1CCOCC1.O>CN1CCCC1=O>[Br:16][C:17]1[CH:26]=[C:25]2[C:20]([CH2:21][CH2:22][N:23]([C:2]3[CH:7]=[C:6]([N:8]4[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]4)[N:5]=[C:4]([NH2:15])[N:3]=3)[CH2:24]2)=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 962WaterHCID 79724-MethylmorpholineHCID 14845194-Chloro-6-(4-methylpiperazin-1-yl)pyrimidin-2-amineHCID 107292557-Bromo-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 467010484-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amineYield 78.5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 4-chloro-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (500.0 mg, 2.196 mmol), 7-bromo-1,2,3,4-tetrahydroisoquinoline (512.3 mg, 2.416 mmol, Alfa Aesar, Cat. No. B25712) and 4-methylmorpholine (289.7 μL, 2.635 mmol) in N-methylpyrrolidinone (10 mL) was heated at 180° C. overnight. The reaction mixture was cooled to r.t., poured into water, extracted with AcOEt, washed with brine, dried with MgSO4, filtered, and concentrated. The residue was purified by flash chromatograph on a silica gel column using 10% MeOH in CH2Cl2 (include 1% NH3) as eluent to afford the desired compound 695 mg (yield 78.5%). LCMS (M+H)+: m/z=403.2.

Workup

  1. extractionextracted with AcOEt
  2. washwashed with brine
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatograph on a silica gel column

Sources & evidence

ORD record
ord-0be5fe84a5ce44bb950329907c35bbbf
Source dataset
uspto-grants-2013_05
Patent number
US08436008B2

Reaction notes

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