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Morpholine → 2-[2-({3-[4-(morpholine-4-carbonyl)phenoxy]propyl}-pyridin-4-ylmethylamino)ethyl]-2H-isoquinolin-1-one dihydrochloride

HRID 1504184
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HRID 1504184 반응식
Br[C:2]1[CH:32]=[CH:31][C:5]([O:6][CH2:7][CH2:8][CH2:9][N:10]([CH2:24][C:25]2[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=2)[CH2:11][CH2:12][N:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]2=[O:23])=[CH:4][CH:3]=1.[C:33](=[O:36])([O-])[O-].[Na+].[Na+].[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.C(OC(=O)C)C.[ClH:51]>C(=[Mo](=C=O)(=C=O)(=C=O)(=C=O)=C=O)=O.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd].C(OCC)(=O)C.O.C1COCC1>[ClH:51].[ClH:51].[N:39]1([C:33]([C:2]2[CH:3]=[CH:4][C:5]([O:6][CH2:7][CH2:8][CH2:9][N:10]([CH2:24][C:25]3[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=3)[CH2:11][CH2:12][N:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:14]3=[O:23])=[CH:31][CH:32]=2)=[O:36])[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1
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참가 물질

10

반응물 4

HCID 8083MorpholineHCID 10340Sodium CarbonateHCID 21866389Hydrogen chloride-ethyl acetateHCID 669599672-(2-{[3-(4-Bromophenoxy)propyl]pyridin-4-ylmethylamino}ethyl)-2H-isoquinolin-1-one

생성물 1

HCID 669600602-[2-({3-[4-(morpholine-4-carbonyl)phenoxy]propyl}-pyridin-4-ylmethylamino)ethyl]-2H-isoquinolin-1-one dihydrochloride

시약·촉매·용매 5

HCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)촉매HCID 178521658HCID 178521658, 화합물촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매2회

반응 조건

온도
170 °C

실험 절차

2-(2-{[3-(4-Bromophenoxy)propyl]pyridin-4-ylmethylamino}ethyl)-2H-isoquinolin-1-one(500 mg), hexacarbonyl molybdenum(264 mg), trans-di-μ-acetatobis[2-(di-o-tolylphosphino)benzyl]dipalladium (II) (Herrmann's palladacycle) (23 mg), sodium carbonate(318 mg), and morpholine(0.26 ml) were added to THF(5 ml). The mixture was heated at 170° C. for 10 minutes (microwave reactor). The reaction mixture was cooled to room temperature. Water and ethyl acetate were added thereto, followed by celite filtration. The organic layer was dried with sodium sulfate, and condensed under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate: methanol=1:0→7:3). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution was added to an ethyl acetate solution of the residue. The precipitated insoluble matter was separated, washed with ethyl acetate, and dried to give the title compound(150 mg) as a white powder.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfollowed by celite filtration
  3. dry with materialThe organic layer was dried with sodium sulfate, and condensed under reduced pressure
  4. customThe residue was purified by NH silica gel column chromatography (ethyl acetate: methanol=1:0→7:3)
  5. customcondensed under reduced pressure
  6. customThe precipitated insoluble matter was separated
  7. washwashed with ethyl acetate
  8. customdried

출처 및 근거

ORD 기록
ord-0b6ef63afbe44ef496d989adef40d42d
출처 데이터셋
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09212187B2

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