2-Fluoro-4-nitrophenol → 3-Fluoro-4-(2-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yloxy)benzenamine

HRID 2117136Notes

Reaction equation

Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:9]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)=[CH:10][C:3]=12.[F:25][C:26]1[CH:31]=[C:30]([N+:32]([O-])=O)[CH:29]=[CH:28][C:27]=1[OH:35].CCN(C(C)C)C(C)C>CN1C(=O)CCC1.CCOC(C)=O>[F:25][C:26]1[CH:31]=[C:30]([NH2:32])[CH:29]=[CH:28][C:27]=1[O:35][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:9]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)=[CH:10][C:3]=12

Participants

Conditions

Temperature: 185 °C

Procedure

A mixture of 4-chloro-2-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine (3.2 g, 8.9 mmol), 2-fluoro-4-nitrophenol (2.79 g, 17.8 mmol), and DIPEA (3.5 mL, 20 mmol) in NMP (15 mL) was heated in a sealed tube at 185° C. for 3 days. The mixture was diluted with EtOAc and filtered through a short pad of Celite® (EtOAc). The filtrate was washed with 5% aq. Na2CO3 solution and dried over MgSO4. The title compound was purified by flash column chromatography (silica gel, 100% CH2Cl2 to 50% EtOAc/CH2Cl2) to afford the desired product (295 mg, 7.4%) as a light brown solid. LC/MS(ESI+) m/z 451 (M+H)+.

Workup

filtrationfiltered through a short pad of Celite® (EtOAc)
washThe filtrate was washed with 5% aq. Na2CO3 solution
dry with materialdried over MgSO4
customThe title compound was purified by flash column chromatography (silica gel, 100% CH2Cl2 to 50% EtOAc/CH2Cl2)

Sources & evidence

ORD record: ord-44ba9985d232490cab86580524ca2393
Source dataset: uspto-grants-2008_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07439246B2

Reaction notes

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