Potassium Phosphate, Tribasic → Acetic acid 2-(6-dimethylamino-1-oxo-1H-isoquinolin-2-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzyl ester

HRID 2245653

반응식

HRID 2245653 반응식
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[O:25])=[CH:20][N:19]=2)[C:3]1=[O:32].Br[C:34]1[CH:44]=[CH:43][CH:42]=[C:41]([N:45]2[CH:54]=[CH:53][C:52]3[C:47](=[CH:48][CH:49]=[C:50]([N:55]([CH3:57])[CH3:56])[CH:51]=3)[C:46]2=[O:58])[C:35]=1[CH2:36][O:37][C:38](=[O:40])[CH3:39].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>>[CH3:57][N:55]([CH3:56])[C:50]1[CH:51]=[C:52]2[C:47](=[CH:48][CH:49]=1)[C:46](=[O:58])[N:45]([C:41]1[CH:42]=[CH:43][CH:44]=[C:34]([C:6]3[CH:5]=[C:4]([NH:17][C:18]4[CH:23]=[CH:22][C:21]([C:24]([N:26]5[CH2:27][CH2:28][O:29][CH2:30][CH2:31]5)=[O:25])=[CH:20][N:19]=4)[C:3](=[O:32])[N:2]([CH3:1])[CH:7]=3)[C:35]=1[CH2:36][O:37][C:38](=[O:40])[CH3:39])[CH:54]=[CH:53]2

참가 물질

4

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 59216403Acetic acid 2-bromo-6-(6-dimethylamino-1-oxo-1H-isoquinolin-2-yl)-benzyl esterHCID 592164661-Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one

생성물 1

HCID 59216499Acetic acid 2-(6-dimethylamino-1-oxo-1H-isoquinolin-2-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzyl ester수율 52.6%

반응 조건

온도
100 °C

실험 절차

To 1-Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one (43 mg, 0.097 mmol), Acetic acid 2-bromo-6-(6-dimethylamino-1-oxo-1H-isoquinolin-2-yl)-benzyl ester (40 mg, 0.097 mmol), potassium phosphate (41 mg, 0.19 mmol), 2-(dicyclohexylphoshphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (2.7 mg, 0.0057 mmol), and bis(dibenzylidineacetone)palladium(0) (1.6 mg, 0.0028 mmol) was added 4 mL of degassed 1:3 water/n-butanol. The headspace of the vessel was evacuated and backfilled with argon 4 times. This was heated at 100° C. for 110 minutes. This was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by flash chromatography (gradient elution 2 to 5% methanol/dichloromethane) to yield Acetic acid 2-(6-dimethylamino-1-oxo-1H-isoquinolin-2-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzyl ester (33 mg, 0.051 mmol). MS (ESI) 649.2 (M+H)+.

후처리

  1. customof degassed 1:3 water/n-butanol
  2. customThe headspace of the vessel was evacuated
  3. customThis was partitioned between ethyl acetate and water
  4. washThe ethyl acetate layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. custompurified by flash chromatography (gradient elution 2 to 5% methanol/dichloromethane)

출처 및 근거

ORD 기록
ord-1ac306e4b629408d830d8812cfe2e08b
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07683064B2

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