Potassium Phosphate, Tribasic → US10023592, Example 369

HRID 575802Notes

Reaction equation

HRID 575802 reaction equation
[F:1][C:2]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][S:12]([CH2:15][CH3:16])(=[O:14])=[O:13])=[CH:7][C:6]=1B1OC(C)(C)C(C)(C)O1.Br[C:32]1[N:37]2[CH:38]=[N:39][CH:40]=[C:36]2[C:35](=[O:41])[N:34]([CH3:42])[CH:33]=1.[O-]P([O-])([O-])=O.[K+].[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]>[F:1][C:2]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][S:12]([CH2:15][CH3:16])(=[O:13])=[O:14])=[CH:7][C:6]=1[C:32]1[N:37]2[CH:38]=[N:39][CH:40]=[C:36]2[C:35](=[O:41])[N:34]([CH3:42])[CH:33]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 1180225995-Bromo-7-methylimidazo[1,5-a]pyrazin-8(7h)-oneHCID 1239573972-[2-(2,4-Difluorophenoxy)-5-(ethylsulfonylmethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 118021617US10023592, Example 369Yield 45%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of the title compound from Step 1 (150 mg, 0.34 mmol), the title compound from Example 129 Step 1 (87 mg, 0.38 mmol), K3PO4 (217 mg, 1.02 mmol) and Pd(dppf)Cl2 (22 mg, 0.03 mmol) in dioxane (5 mL) and H2O (1 mL) was stirred at 70° C. for 18 hrs under N2. The resulting mixture was filtered and concentrated. The residue was purified by prep-HPLC to give the title compound (70.0 mg, 45%) as a yellow solid. 1H NMR (DMSO-d6, 400 MHz) δ 8.83 (s, 1H), 8.33 (s, 1H), 7.64 (d, J=2.0 Hz, 1H), 7.57 (dd, J1=8.8 Hz, J2=2.0 Hz, 1H), 7.53-7.41 (m, 2H), 7.37 (s, 1H), 7.20-7.12 (m, 1H), 6.93 (d, J=8.8 Hz, 1H), 4.54 (s, 2H), 3.45 (s, 3H), 3.09 (q, J=7.6 Hz, 2H), 1.23 (t, J=7.6 Hz, 3H). LCMS: 460.1 (M+1)+

Workup

  1. filtrationThe resulting mixture was filtered
  2. concentrationconcentrated
  3. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-96d6124579704e05aea42521e1eac719
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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