Methyl iodide → Ethyl 4-((5-bromopyrimidin-2-yl)(methyl)amino)-1-methylcyclohexanecarboxylate

HRID 712248Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[N:4][C:5]([NH:8][CH:9]2[CH2:14][CH2:13][C:12]([CH3:20])([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:11][CH2:10]2)=[N:6][CH:7]=1.[H-].[Na+].CI.[CH3:25]CCCCC>C1COCC1>[Br:1][C:2]1[CH:7]=[N:6][C:5]([N:8]([CH3:25])[CH:9]2[CH2:10][CH2:11][C:12]([CH3:20])([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:13][CH2:14]2)=[N:4][CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To an ice-cold solution of ethyl 4-(5-bromopyrimidin-2-ylamino)-1-methylcyclohexanecarboxylate (0.30 g, 0.88 mmol) in THF (10 mL) was added NaH (0.053 g, 1.32 mmol, 60% dispersion in mineral oil) portion wise and the mixture stirred at 0° C. for 10 min followed by drop wise addition of MeI (0.066 ml, 1.06 mmol). The mixture was heated up to 65° C. for 6-8 h. After completion (by TLC), the reaction was cooled up to 0° C. and quenched with ice-cold water (20 mL), extracted with EtOAc (2×50 mL) and the combined organics washed with water, brine and dried over Na2SO4. The crude residue was purified over 100-200 M silica-gel using 2% EtOAc:hexane to obtain the desired product as a yellow liquid (0.074 g, 24% yield). 1H NMR (DMSO-d6): δ 8.42 (s, 2H), 4.51 (m, 1H), 4.15 (q, J=6.80 Hz, 2H), 2.85 (s, 3H), 2.15 (m, 2H), 1.52 (m, 4H), 1.36 (m, 2H), 1.29 (t, J=6.80 Hz, 3H) and 1.21 (s, 3H).

Workup

temperatureThe mixture was heated up to 65° C. for 6-8 h
temperatureAfter completion (by TLC), the reaction was cooled up to 0° C.
customquenched with ice-cold water (20 mL)
extractionextracted with EtOAc (2×50 mL)
washthe combined organics washed with water, brine
dry with materialdried over Na2SO4
customThe crude residue was purified over 100-200 M silica-gel

Sources & evidence

ORD record: ord-15c0ac79be2e491bb133378f10929844
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181234B2

Reaction notes

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