Sodium Carbonate → HCID 118022608, compound

HRID 518560Notes

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, 1 H), 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-d1ae55d25cae4318a441c09db43c7a9d
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115114B2

Reaction notes

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