Ethyl Acetate → 4-[2-Methoxy-5-[2-(oxan-2-yloxy)ethylsulfonyl]phenyl]-2-methyl-6-(1-methylpyrazol-4-yl)isoquinolin-1-one

HRID 575684Notes

Reaction equation

HRID 575684 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([CH2:12][CH2:13][O:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)(=[O:11])=[O:10])=[CH:5][C:4]=1B1OC(C)(C)C(C)(C)O1.Br[C:31]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([C:41]3[CH:42]=[N:43][N:44]([CH3:46])[CH:45]=3)[CH:39]=2)[C:34](=[O:47])[N:33]([CH3:48])[CH:32]=1.C(O[K])(C)=O.CC(=O)OCC>O1CCOCC1.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]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([CH2:12][CH2:13][O:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)(=[O:10])=[O:11])=[CH:5][C:4]=1[C:31]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([C:41]3[CH:42]=[N:43][N:44]([CH3:46])[CH:45]=3)[CH:39]=2)[C:34](=[O:47])[N:33]([CH3:48])[CH:32]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 1180215864-Bromo-2-methyl-6-(1-methylpyrazol-4-yl)isoquinolin-1-oneHCID 1235269572-[2-Methoxy-5-[2-(oxan-2-yloxy)ethylsulfonyl]phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 178476685HCID 178476685, compound

Product 1

HCID 1180220574-[2-Methoxy-5-[2-(oxan-2-yloxy)ethylsulfonyl]phenyl]-2-methyl-6-(1-methylpyrazol-4-yl)isoquinolin-1-oneYield 23.6%

Reagents, catalysts & solvents 2

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

Procedure

The title compound of step 5 (325 mg, 0.76 mmol), the title compound of Example 41, step 2 (201 mg, 0.64 mmol), Pd(dppf)Cl2 (66 mg, 0.08 mmol) and AcOK (125 mg, 1.28 mmol) in 1,4-dioxane (6 mL) were heated at 70° C. for 12 h. After silica gel column chromatography (PE:EA=5:1-0:1) the title compound (80 mg, 23.6%) was obtained as a gray solid. 1H NMR: (CDCl3, 400 MHz) δ 8.48 (d, J=8.4 Hz, 1H), 8.03 (dd, J1=8.8 Hz, J2=2.4 Hz, 1H), 7.88 (d, J=2.4 Hz, 1H), 7.58-7.69 (m, 2H), 7.14-7.18 (m, 2H), 7.06 (s, 1H), 4.50 (t, J=4.4 Hz, 2H), 4.06-4.15 (m, 1H), 3.93 (s, 3H), 3.84-3.90 (m, 1H), 3.84 (s, 3H), 3.71-3.80 (m, 2H), 3.65 (s, 3H), 3.49 (t, J=5.6 Hz, 2H), 3.41-3.47 (m, 1H), 1.25-1.67 (m, 6H). LCMS: 538.2 (M+H)+; 454.1 (M+H-THP)+.

Sources & evidence

ORD record
ord-5ef87b3ca92c4f0382ecb5627d2557e7
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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