Methyl iodide → HCID 66845230, compound

HRID 1916430Notes

Reaction equation

[OH:1][C@H:2]1[C:6]2[N:7]=[CH:8][N:9]=[C:10]([N:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[C:5]=2[C@H:4]([CH3:24])[CH2:3]1.[H-].[Na+].[CH3:27]I>CN(C=O)C>[CH3:27][O:1][C@H:2]1[C:6]2[N:7]=[CH:8][N:9]=[C:10]([N:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[C:5]=2[C@H:4]([CH3:24])[CH2:3]1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of tert-butyl 4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate in DMF (2 mL) was added dropwise to a suspension of NaH (50 mg, 1.98 mmol) in DMF (5 mL) at 0° C. A solution of methyl iodide (700 mg, 5 mmol) in DMF (1 mL) was then added dropwise. The reaction mixture was stirred at 0° C. for 1 hour. The reaction was quenched with ice/saturated NH4Cl, extracted with DCM (2×10 mL). The combined organics were dried (Na2SO4), filtered and concentrated to afford tert-butyl 4-((5R,7R)-7-methoxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate as an oil, which was used without purification. MS (APCI+) [M+H]+ 349.0. This material was used to prepare the title compound as described analogously in Example 3, Steps 12-14, substituting the appropriate starting materials. m/z 504.3; 1H NMR (400 MHz, D2O) d ppm 8.49 (s, 1H), 7.81 (d, J=8.4 Hz, 2H), 7.58 (d, J=8.4 Hz, 2H), 5.16 (t, J=7.6 Hz, 1H), 4.49-3.61 (m, 10H), 3.47 (s, 3H), 3.38-3.33 (m, 3H), 2.37-1.78 (m, 6H), 1.36-1.32 (m, 2H), 1.08 (d, J=6.8 Hz, 3H).

Workup

customThe reaction was quenched with ice/saturated NH4Cl
extractionextracted with DCM (2×10 mL)
dry with materialThe combined organics were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-6c6dcc28ebe6436b8aca75c76315376f
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08618097B2

Reaction notes

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