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

Reaction equation

HRID 519151 reaction equation
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

Participants

7

Reactant 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

Product 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-oneYield 68.3%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

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]+.

Workup

  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)

Sources & evidence

ORD record
ord-0051746ef95d4415af4019d2eb083481
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Linked notes

Loading…