Sodium hydride → HCID 117778937, compound

HRID 1527026Notes

Reaction equation

[CH3:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.[H-].[Na+].Br[CH:19]([C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=1)[CH3:20]>CN(C=O)C.O>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([CH:19]([N:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:2]2[CH3:1])[CH3:20])=[CH:22][CH:23]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of ethyl 2-methyl-1H-indole-3-carboxylate (250 mg, 1.23 mmol) in anhydrous DMF (2 mL) was added NaH (60% in mineral oil, 74 mg, 1.85 mmol) at room temperature under N2. The reaction was stirred at 50-60° C. for 30 min. Then the reaction was cooled to 0° C. and a solution of 1-(1-bromoethyl)-4-chlorobenzene (from Example 35; 400 mg, 1.85 mmol) in DMF (1 mL) was added drop-wise. The reaction was stirred at room temperature overnight. Then the mixture was diluted with water and extracted with EtOAc. The organic extract was combined, dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography using an eluent of petroleum ether/EtOAc (60:1) to afford the title compound as a yellow oil. (210 mg, yield 50.1%) 1H NMR (Methanol-d4, 400 MHz) δ 8.07-8.04 (m, 1H), 7.33-7.29 (m, 2H), 7.16-7.15 (m, 2H), 7.14-7.08 (m, 1H), 7.07-6.96 (m, 2H), 5.97 (q, J=7.2 Hz, J2=14.4 Hz, 1H), 4.37 (d, J=7.2 Hz, 2H), 2.76 (m, 3H), 1.95 (d, J=6.8 Hz, 3H), 1.43 (d, J=14.0 Hz, 3H).

Workup

temperatureThen the reaction was cooled to 0° C.
stirringThe reaction was stirred at room temperature overnight
extractionextracted with EtOAc
extractionThe organic extract
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record: ord-ccc580ae8d0b4841a5e6a93a11050a89
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085583B2

Reaction notes

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