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

HRID 272988

반응식

HRID 272988 반응식
[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

참가 물질

5

반응물 3

HCID 784901,4-Dichlorophthalazine2회HCID 81531DiisopropylethylamineHCID 11645410(4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-69a73dbbb7d44e70b14512f6dfdb8b64
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07456164B2

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