Methyl iodide → HCID 68291689, compound

HRID 877743Notes

Reaction equation

HRID 877743 reaction equation
[CH3:1][C@@H:2]1[C@@H:9]2[C@@H:5]([CH2:6][N:7]([S:10]([CH3:13])(=[O:12])=[O:11])[CH2:8]2)[CH2:4][C@H:3]1[NH:14][C:15]1[C:16]2[N:17]([CH:24]=[C:25]([C:27]3[NH:31][N:30]=[N:29][N:28]=3)[CH:26]=2)[N:18]=[CH:19][C:20]=1[C:21]([NH2:23])=[O:22].IC.[C:34](=O)([O-])[O-].[K+].[K+]>CN1CCCC1=O>[CH3:1][C@@H:2]1[C@@H:9]2[C@@H:5]([CH2:6][N:7]([S:10]([CH3:13])(=[O:12])=[O:11])[CH2:8]2)[CH2:4][C@H:3]1[NH:14][C:15]1[C:16]2[N:17]([CH:24]=[C:25]([C:27]3[N:28]=[N:29][N:30]([CH3:34])[N:31]=3)[CH:26]=2)[N:18]=[CH:19][C:20]=1[C:21]([NH2:23])=[O:22]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 178461483HCID 178461483, compound

Product 1

HCID 68291689HCID 68291689, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of the crude 4-(((3aS,4R,5R,6aS)-4-methyl-2-(methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-yl)amino)-6-(1H-tetrazol-5-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide from Step 2, iodomethane (6.8 μl, 0.109 mmol) and potassium carbonate (23.2 mg, 0.168 mmol) in 1-methyl-2-pyrrolidinone (1 mL) was stirred at room temperature for 2 h. Attempted purification by RP-HPLC gave impure product. The mixture was further purified by silica gel chromatography, eluting with 0 to 10% methanol in dichloromethane to give the title compound (4 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.92 (d, J=7.3 Hz, 1H), 8.30 (s, 1H), 8.20 (d, J=1.5 Hz, 1H), 7.40 (d, J=1.5 Hz, 1H), 5.91-5.90 (m, 1H), 4.40 (s, 3H), 4.28-4.05 (m, 1H), 3.35-3.13 (m, 4H), 2.93 (s, 3H), 2.90-2.75 (m, 1H), 2.62-2.55 (m, 1H), 2.46-2.30 (m, 1H), 1.66-1.54 (m, 1H), 1.39-1.29 (m, 1H), 1.08 (d, J=6.6 Hz, 3H); MS (ES+) m/z: 460.3 (M+H); LC retention time: 6.988 min (analytical HPLC Method E).

Workup

  1. custompurification by RP-HPLC
  2. customgave impure product
  3. customThe mixture was further purified by silica gel chromatography
  4. washeluting with 0 to 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-24df3f0f7e3447c2bded41cb4feb2952
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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