Potassium Carbonate → (R)-6-(1,3-Dimethyl-azetidin-3-ylamino)-7-((E)-2-ethoxy-vinyl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

HRID 519151노트

반응식

HRID 519151 반응식
Br[C:2]1[CH:15]=[C:14]2[C:5]([N:6]3[C:11]([CH2:12][O:13]2)=[N:10][NH:9][C:8](=[O:16])[C@H:7]3[CH3:17])=[CH:4][C:3]=1[NH:18][C:19]1([CH3:24])[CH2:22][N:21]([CH3:23])[CH2:20]1.[CH2:25]([O:27]/[CH:28]=[CH:29]/B1OC(C)(C)C(C)(C)O1)[CH3:26].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH3:23][N:21]1[CH2:22][C:19]([NH:18][C:3]2[CH:4]=[C:5]3[C:14](=[CH:15][C:2]=2/[CH:26]=[CH:25]/[O:27][CH2:28][CH3:29])[O:13][CH2:12][C:11]2[N:6]3[C@H:7]([CH3:17])[C:8](=[O:16])[NH:9][N:10]=2)([CH3:24])[CH2:20]1

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 219739081-Ethoxyethene-2-boronic acid pinacol esterHCID 86727543(R)-7-bromo-6-(1,3-dimethyl-azetidin-3-ylamino)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

생성물 1

HCID 86727544(R)-6-(1,3-Dimethyl-azetidin-3-ylamino)-7-((E)-2-ethoxy-vinyl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one수율 68.3%

시약·촉매·용매 3

HCID 178418807HCID 178418807, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

To a solution of (R)-7-bromo-6-(1,3-dimethyl-azetidin-3-ylamino)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (1.2 g, 3.04 mmol) and (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.66 g, 3.35 mmol) in a mixture of dioxane (12 mL) and water (2 mL) was added PdCl2(dppf)-CH2Cl2 adduct (0.25 g, 0.30 mmol) and K2CO3 (0.842 g, 6.09 mmol). The mixture was stirred at 100° C. for 3 h. The mixture was cooled to ambient temperature and the solvent was removed in vacuo to give the residue product, which was purified by chromatography on silica gel (eluting with 10% MeOH in dichloromethane) to give (R)-6-(1,3-dimethyl-azetidin-3-ylamino)-7-((E)-2-ethoxy-vinyl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.8 g, 68%) 1H NMR (400 MHz, CDCl3) δ=8.20 (s, 1H), 6.80 (s, 1H), 6.71 (d, J=12.4 Hz, 1H), 5.90 (s, 1H), 5.64 (d, J=12.4 Hz, 1H), 4.63-4.46 (m, 3H), 3.91 (q, J=6.8 Hz, 2H), 3.53 (m, 2H), 3.27 (m, 2H), 2.43 (s, 3H), 1.61 (s, 3H), 1.50 (d, J=6.8 Hz, 3H), 1.35 (t, J=6.8 Hz, 3H). LC/MS (Table 1, Method 2) Rt=0.889 min; MS m/z: 386 [M+H]+.

후처리

  1. temperatureThe mixture was cooled to ambient temperature
  2. customthe solvent was removed in vacuo
  3. customto give the residue product, which
  4. customwas purified by chromatography on silica gel (eluting with 10% MeOH in dichloromethane)

출처 및 근거

ORD 기록
ord-0051746ef95d4415af4019d2eb083481
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115151B2

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