Methyl iodide → HCID 66589545, compound

HRID 340405Notes

Reaction equation

[CH2:1]1[C:13]2[C:12]3[CH:11]=[C:10]([C:14]([O:16][CH3:17])=[O:15])[CH:9]=[CH:8][C:7]=3[NH:6][C:5]=2[CH2:4][CH2:3][N:2]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].[H-].[Na+].I[CH3:28].[NH4+].[Cl-]>CN(C=O)C>[CH3:28][N:6]1[C:7]2[CH:8]=[CH:9][C:10]([C:14]([O:16][CH3:17])=[O:15])=[CH:11][C:12]=2[C:13]2[CH2:1][N:2]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:3][CH2:4][C:5]1=2

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 2-tert-butyl 8-methyl 3,4-dihydro-1H-pyrido[4,3-b]indole-2,8(5H)-dicarboxylate (17 in Scheme 1(i), 1.0 g, 3.0 mmol) in DMF (6.0 mL) was added to a cold solution (ice bath) of NaH (60%, 121 mg, 3.0 mmol) in DMF (3 mL). After stirring at 0° C. under N2 atmosphere for 30 min, iodomethane (210 μL, 471 mg, 3.3 mmol) was added dropwise. The reaction mixture was then allowed to warm up to room temperature overnight, cooled down to 0° C. and poured into saturated NH4Cl solution (20 mL). The resulting brown precipitate was filtered, dried and chromatographed (neat DCM→2% MeOH/DCM) to provide, upon trituration with ethyl ether, 2-tert-butyl 8-methyl 5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2,8(5H)-dicarboxylate (18 in Scheme 1(i), 0.82 g, 79%). 1H NMR (CD3OD, 300 MHz) 8.13 (s, 1H), 7.82 (dd, J=8.8, 1.7 Hz, 1H), 7.38 (d, J=8.5 Hz, 1H), 4.64 (br s, 2H), 3.90 (s, 3H), 3.84 (t, J=5.6 Hz, 2H), 3.69 (s, 3H), 2.86 (t, J=5.6 Hz, 2H), 1.52 (s, 9H) ppm; MS (ES) 345 (M+H).

Workup

temperatureto warm up to room temperature overnight
temperaturecooled down to 0° C.
filtrationThe resulting brown precipitate was filtered
customdried
customchromatographed (neat DCM→2% MeOH/DCM)

Sources & evidence

ORD record: ord-3c29277329554224bd75cfcab5ec95c4
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08895578B2

Reaction notes

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