Sodium Carbonate → HCID 118022608, compound

HRID 575826Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([CH2:8][S:9]([CH2:12][CH3:13])(=[O:11])=[O:10])[CH:5]=[CH:4][C:3]=1[O:14][CH2:15][C:16]([F:19])([F:18])[F:17].[CH3:20][N:21]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22]1=[O:40].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:12]([S:9]([CH2:8][C:6]1[CH:5]=[CH:4][C:3]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[C:2]([C:29]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22](=[O:40])[N:21]([CH3:20])[CH:30]=2)[CH:7]=1)(=[O:11])=[O:10])[CH3:13]

Participants

Conditions

Temperature: 70 °C

Procedure

The title compound from Step 5 (200 mg, 0.58 mmol), 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-one (197 mg, 0.69 mmol), Pd(PPh3)4 (67 mg, 58.0 umol) and Na2CO3 (184 mg, 1.74 mmol) in dioxane (6 mL) and water (6 drops) was degassed and then heated to 70° C. for 18 hours under N2. The reaction mixture was concentrated under reduced pressure and the residue was purified by column chromatography (PE:EA=5:1˜1:1) followed by prep-HPLC purification to afford the title compound (164.44 mg, 67%) as an off-white solid. 1H NMR (CDCl3, 400 MHz) δ 8.52 (d, J=8.0 Hz, 1H), 7.58-7.48 (m, 3H), 7.40 (d, J=2.4 Hz, 1H), 7.22 (d, J=8.0, 1H), 7.07 (t, J=8.0, 2 H), 4.30 (q, J=8.0 Hz, 2H), 4.23 (s, 2H), 3.67 (s, 3H), 2.98 (q, J=7.6 Hz, 2H), 1.43 (t, J=7.6 Hz, 3H). LCMS: 440.0 (M+1)+

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
customthe residue was purified by column chromatography (PE:EA=5:1˜1:1)
customfollowed by prep-HPLC purification

Sources & evidence

ORD record: ord-8b9559cf77664c249bab2782fd779d70
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034900B2

Reaction notes

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