Tetrahydro-4H-pyran-4-one → 8-Chloro-1-(3,4,5,6-tetrahydro-2h-[1,2']bipyridinyl-4-yl)-5-(tetrahydro-pyran-4-yl)-5,6-dihydro-4h-2,3,5,10b-tetraaza-benzo[e]azulene

HRID 1243575노트

반응식

HRID 1243575 반응식
[O:1]1[CH2:6][CH2:5][C:4](=O)[CH2:3][CH2:2]1.[Cl:8][C:9]1[CH:34]=[CH:33][C:12]2[N:13]3[C:17]([CH2:18][NH:19][CH2:20][C:11]=2[CH:10]=1)=[N:16][N:15]=[C:14]3[CH:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)[CH2:23][CH2:22]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Cl:8][C:9]1[CH:34]=[CH:33][C:12]2[N:13]3[C:17]([CH2:18][N:19]([CH:4]4[CH2:5][CH2:6][O:1][CH2:2][CH2:3]4)[CH2:20][C:11]=2[CH:10]=1)=[N:16][N:15]=[C:14]3[CH:21]1[CH2:22][CH2:23][N:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)[CH2:25][CH2:26]1

참가 물질

5

반응물 3

HCID 121599Tetrahydro-4H-pyran-4-one2회HCID 5049666Sodium triacetoxyborohydride2회HCID 113264888-Chloro-1-(3,4,5,6-tetrahydro-2h-[1,2']bipyridinyl-4-yl)-5,6-dihydro4h-2,3,5,10b-tetraaza-benzo[e]azulene

생성물 1

HCID 219255668-Chloro-1-(3,4,5,6-tetrahydro-2h-[1,2']bipyridinyl-4-yl)-5-(tetrahydro-pyran-4-yl)-5,6-dihydro-4h-2,3,5,10b-tetraaza-benzo[e]azulene수율 50.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
40 °C

실험 절차

Tetrahydro-pyran-4-one (68 mg, 0.68 mmol) was added to a solution of the amine of example 4 (130 mg, 0.34 mmol) in dichloromethane (5 ml). The mixture was stirred at room temperature for 0.25 hours before sodium triacetoxyborohydride (217 mg, 1.0 mmol) was added, and the reaction mixture was stirred for a further 18 hours. Further tetrahydro-pyran-4-one (68 mg, 0.68 mmol) and sodium triacetoxyborohydride (217 mg, 1.0 mmol) were added and the reaction mixture was heated to 40° C. for 24 hours. The reaction mixture was partitioned between 2N aqueous sodium carbonate solution (10 ml) and ethyl acetate (50 ml). The organic layer was washed three times with 2N aqueous sodium carbonate solution (10 ml), once with saturated aqueous brine, and then dried over magnesium sulphate before filtering and evaporating the filtrate under reduced pressure. The residue was purified by chromatography on silica gel using a gradient of ethyl acetate in pentane (0% to 30%) as eluant, followed by chromatography on silica gel using a gradient of methanol in dichloromethane (0% to 5%) as eluant, to afford the title compound as a brown foam (80 mg).

후처리

  1. additionwas added
  2. customThe reaction mixture was partitioned between 2N aqueous sodium carbonate solution (10 ml) and ethyl acetate (50 ml)
  3. washThe organic layer was washed three times with 2N aqueous sodium carbonate solution (10 ml)
  4. dry with materialonce with saturated aqueous brine, and then dried over magnesium sulphate
  5. filtrationbefore filtering
  6. customevaporating the filtrate under reduced pressure
  7. customThe residue was purified by chromatography on silica gel using a gradient of ethyl acetate in pentane (0% to 30%) as eluant

출처 및 근거

ORD 기록
ord-47c32d0be63a446ba2de309b7edeee1f
출처 데이터셋
uspto-grants-2006_10
특허 번호
US07119088B2

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