Iodine → 1-Cyclobutyl-2-iodo-6-(pyrimidin-2-yloxy)-1h-indole-3-carbonitrile

HRID 502297Notes

Reaction equation

[CH:1]1([N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([OH:14])[CH:12]=3)[C:7]([C:15]#[N:16])=[CH:6]2)[CH2:4][CH2:3][CH2:2]1.[Li+].CC([N-]C(C)C)C.[I:25]I.C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:34]1[N:39]=[CH:38][CH:37]=[CH:36][N:35]=1>C1COCC1.CN(C=O)C>[CH:1]1([N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([O:14][C:34]4[N:39]=[CH:38][CH:37]=[CH:36][N:35]=4)[CH:12]=3)[C:7]([C:15]#[N:16])=[C:6]2[I:25])[CH2:2][CH2:3][CH2:4]1

Participants

Conditions

Temperature: -78 °C

Procedure

T6 a solution of 1-cyclobutyl-6-hydroxy-1H-indole-3-carbonitrile (4.24 g, 20 mmol) in THF (60.0 mL) at −78° C. was added LDA (30.7 mL, 46.0 mmol) and iodine (7.62 g, 30.0 mmol). The mixture was stirred at −78° C. for 10 min, warmed to room temperature and stirred for 3 h. The reaction mixture was poured into ice-water (500 mL) and the precipitate was filtered and washed with water and CH2Cl2. After drying in air the crude iodide obtained (3.99 g) was taken up in DMF (25 mL) and Cs2CO3 (9.78 g, 30.0 mmol) and 2-chloropyrimidine (2.18 g, 19.0 mmol) were added to this solution. The mixture was stirred at 70° C. for 30 min, poured into ice water (200 mL) and the precipitate was collected on a filter, washed with water and purified on silica gel (CH2Cl2/EtOAc, 9.75:0.25) to provide 1-cyclobutyl-2-iodo-6-(pyrimidin-2-yloxy)-1H-indole-3-carbonitrile (1.52 g, 47%).

Workup

temperaturewarmed to room temperature
stirringstirred for 3 h
filtrationthe precipitate was filtered
washwashed with water and CH2Cl2
dry with materialAfter drying in air the crude iodide
customobtained (3.99 g)
stirringThe mixture was stirred at 70° C. for 30 min
customthe precipitate was collected on a filter
washwashed with water
custompurified on silica gel (CH2Cl2/EtOAc, 9.75:0.25)

Sources & evidence

ORD record: ord-d3130b2299794e4db5b3fbff0628032c
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772271B2

Reaction notes

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