1,4-Dichlorophthalazine → 4-chloro-N-({4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)phthalazin-1-amine

HRID 272988

Reaction equation

HRID 272988 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH2:22][NH2:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:24][C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:28](Cl)=[N:27][N:26]=1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[Cl:24][C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:28]([NH:23][CH2:22][C:16]2([C:13]3[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][CH2:6][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:11][CH:12]=3)[CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)=[N:27][N:26]=1

Participants

5

Reactant 3

HCID 784901,4-Dichlorophthalazine2×HCID 81531DiisopropylethylamineHCID 11645410(4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine

Product 1

HCID 866019064-chloro-N-({4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)phthalazin-1-amineYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of {4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine (300 mg, 0.94 mmol), 1,4-dichlorophthalazine (188 mg, 0.94 mmol) and N,N-diisopropylethylamine (410 μl, 2.36 mmol) in N,N-dimethylformamide (1 ml) was stirred at room temperature for 18 hours. More 1,4-dichlorophthalazine (188 mg, 0.94 mmol) was added and the reaction stirred at room temperature for 36 hours, then heated at 55° C. for 18 hours. The reaction mixture was partitioned between ethyl acetate (20 ml) and saturated aqueous sodium bicarbonate solution (20 ml). The organic layer was washed with more aqueous sodium bicarbonate, brine, dried over sodium sulphate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (100:0:0 to 92:8:0.8 by volume) to provide the title compound (183 mg, 61%). LRMS APCI+ m/z 481 [M]+.

Workup

  1. stirringthe reaction stirred at room temperature for 36 hours
  2. temperatureheated at 55° C. for 18 hours
  3. customThe reaction mixture was partitioned between ethyl acetate (20 ml) and saturated aqueous sodium bicarbonate solution (20 ml)
  4. washThe organic layer was washed with more aqueous sodium bicarbonate, brine
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (100:0:0 to 92:8:0.8 by volume)

Sources & evidence

ORD record
ord-69a73dbbb7d44e70b14512f6dfdb8b64
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Linked notes

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