Methyl iodide → HCID 178496606, compound

HRID 2389995Notes

Reaction equation

[Br:1][C:2]1[C:3]([NH:16][C@H:17]2[CH2:22][CH2:21][C@H:20]([OH:23])[CH2:19][CH2:18]2)=[N:4][C:5]([N:9]2[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]2[CH3:15])=[N:6][C:7]=1[CH3:8].[H-].[Na+].[CH3:26]I>O1CCCC1>[Br:1][C:2]1[C:3]([NH:16][C@H:17]2[CH2:18][CH2:19][C@H:20]([O:23][CH3:26])[CH2:21][CH2:22]2)=[N:4][C:5]([N:9]2[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]2[CH3:15])=[N:6][C:7]=1[CH3:8]

Participants

Conditions

Temperature: 0 °C

Procedure

To a cooled (0° C.) solution of trans-4-(5-bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-methylpyrimidin-4-ylamino)cyclohexanol (1.45 g, 3.82 mmol) in tetrahydrofuran (40 mL) was added sodium hydride (60% dispersion in oil, 459 mg, 11.5 mmol). After 40 minutes, methyl iodide was added (262 uL, 4.21 mmol) and the mixture was stirred at 0° C. for 2 hours. The ice bath was removed and continued to stir for 3 hours then quenched with methanol and concentrated. The residue was dissolved in ethyl acetate and washed with saturated ammonia chloride (2×), brine, dried (MgSO4), filtered and concentrated. The crude product was purified by flash chromatography eluting with hexanes/methyltertbutyl ether (5-25%) to afford 5-bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)-N-(trans-4-methoxycyclohexyl)-6-methyl pyrimidin-4-amine (1.10 g, 73%).

Workup

customThe ice bath was removed
stirringto stir for 3 hours
customthen quenched with methanol
concentrationconcentrated
dissolutionThe residue was dissolved in ethyl acetate
washwashed with saturated ammonia chloride (2×), brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by flash chromatography
washeluting with hexanes/methyltertbutyl ether (5-25%)

Sources & evidence

ORD record: ord-9769ce444f4348f696c5b4decfe8996b
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08273755B2

Reaction notes

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