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 519151

反応式

HRID 519151 の反応式
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

参加物

7

反応物 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

生成物 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-one収率 68.3%

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-0051746ef95d4415af4019d2eb083481
出典データセット
uspto-grants-2015_08
特許番号
US09115151B2

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