Ethyl Acetate → (1R,2S)-2-(3-((E)-2-(pyridin-3-yl)vinyl)-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-one

HRID 2281784Notes

Reaction equation

I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][N:3]=1.[NH:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]2([CH2:21][CH2:20]2)[C:12]1=[O:22].CC1(C)C(C)(C)OB(/[CH:31]=[CH:32]/[C:33]2[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=2)O1.C(OCC)(=O)C>CN(C=O)C.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>[N:35]1[CH:36]=[CH:37][CH:38]=[C:33](/[CH:32]=[CH:31]/[C:2]2[C:10]3[C:5](=[CH:6][C:7]([C@H:20]4[C@@:13]5([C:14]6[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=6)[NH:11][C:12]5=[O:22])[CH2:21]4)=[CH:8][CH:9]=3)[NH:4][N:3]=2)[CH:34]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of (1R,2S)-2-(3-iodo-1H-indazol-spiro[cyclopropane-1,3′-indolin]-2′-one (50 mg, 0.12 mmol) in DMF (0.4 mL) and water (0.1 mL) was added (E)-3-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)pyridine (50 mg, 0.2 mmol) potassium fluoride (14 mg, 0.24 mmol) and Pd(PPh3)4 (7 mg, 0.006 mmol). The mixture was heated to 120° C. for 2 h under microwave irradiation. Ethyl acetate (50 mL) was added and the solution was washed with water (2×5 mL), brine (5 mL) and dried over MgSO4. Purification by reverse phase preparatory HPLC gave the title compound as a yellow solid (20 mg, 44%).

Workup

washthe solution was washed with water (2×5 mL), brine (5 mL)
dry with materialdried over MgSO4
customPurification by reverse phase preparatory HPLC

Sources & evidence

ORD record: ord-11cbf759c7994866bc14383efbc332da
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139563B2

Reaction notes

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