Potassium Carbonate → HCID 86727601, compound

HRID 519188Notes

Reaction equation

HRID 519188 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[C@@H:18]1[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][C@@H:19]1[CH3:25].[F:26][C:27]1[C:32]([O:33][CH3:34])=[CH:31][CH:30]=[CH:29][C:28]=1B(O)O.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>[CH3:24][N:21]1[CH2:22][CH2:23][C@@H:18]([C:3]2[CH:4]=[C:5]3[C:14](=[CH:15][C:2]=2[C:28]2[CH:29]=[CH:30][CH:31]=[C:32]([O:33][CH3:34])[C:27]=2[F:26])[O:13][CH2:12][C:11]2[N:6]3[C@H:7]([CH3:17])[C:8](=[O:16])[NH:9][N:10]=2)[C@@H:19]([CH3:25])[CH2:20]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 49857442-Fluoro-3-methoxyphenylboronic acidHCID 86727600HCID 86727600, compound

Product 1

HCID 86727601HCID 86727601, compoundYield 45%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

A mixture of (R)-7-bromo-6-((3R,4R)-1,3-dimethyl-piperidin-4-yl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.050 g, 0.123 mmol), (2-fluoro-3-methoxyphenyl)boronic acid (0.025 g, 0.147 mmol), K2CO3 (0.034 g, 0.246 mmol) and PdCl2(dppf)-CH2Cl2 adduct (0.020 g, 0.025 mmol) in dioxane (3 mL) and water (0.5 mL) was stirred at 90° C. overnight. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by preparative TLC (eluting with 17% MeOH in EtOAc) to give (R)-6-((3R,4R)-1,3-dimethyl-piperidin-4-yl)-7-(2-fluoro-3-methoxy-phenyl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.0248 g, 45%) as a solid. 1H NMR (400 MHz, CD3OD): δ 7.14 (m, 2H), 6.96-6.90 (m, 1H), 6.81-6.72 (m, 2H), 4.95-4.91 (m, 1H), 4.60 (d, J=13.2 Hz, 2H), 3.90 (s, 3H), 3.13 (m, 1H), 3.00-2.74 (m, 2H), 2.34 (m, 3H), 2.19 (m, 2H), 2.14 (m, 1H), 1.67 (m, 2H), 1.48 (m, 3H), 0.89-0.79 (m, 3H). LC/MS (Table 1, Method 4) Rt=2.075 min.; MS m/z: 453 [M+H]+. SFC (Table 2, Method 27), Rt=3.239 min.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by preparative TLC (eluting with 17% MeOH in EtOAc)

Sources & evidence

ORD record
ord-309ad47e690c48b4868aead77f59fb25
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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