Methyl iodide → HCID 59341831, compound

HRID 16002

Reaction equation

HRID 16002 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][C:7]([CH2:11][N:12]3[C:20]4[C:15](=[N:16][CH:17]=[C:18]([N:21]5[CH2:25][CH2:24][C@@H:23]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:22]5)[N:19]=4)[N:14]=[N:13]3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[CH3:36]I>O1CCCC1>[CH3:36][N:26]([C@@H:23]1[CH2:24][CH2:25][N:21]([C:18]2[N:19]=[C:20]3[N:12]([CH2:11][C:7]4[CH:6]=[C:5]5[C:10](=[CH:9][CH:8]=4)[N:1]=[CH:2][CH:3]=[CH:4]5)[N:13]=[N:14][C:15]3=[N:16][CH:17]=2)[CH2:22]1)[C:27](=[O:33])[O:28][C:29]([CH3:30])([CH3:32])[CH3:31]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59341797(R)-tert-butyl 1-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyrazin-5-yl)pyrrolidin-3-ylcarbamate

Product 1

HCID 59341831HCID 59341831, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (0° C.) solution of (R)-tert-butyl 1-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyrazin-5-yl)pyrrolidin-3-ylcarbamate (111 mg, 0.249 mmol) in tetrahydrofuran (2.0 mL) was added sodium hydride (60% dispersion in mineral oil, 15 mg, 0.37 mmol). After 30 minutes at 0° C., a solution of methyl iodide (23 uL, 0.37 mmol) in tetrahydrofuran (0.5 mL) was added dropwise over 15 minutes. The reaction mixture was allowed to warm to room temperature as the ice bath melted, stirred overnight, then quenched by adding water (1.0 mL). The tetrahydrofuran was removed in vacuo and the remaining aqueous solution was diluted with ethyl acetate (100 mL). The organic solution was washed with water (20 mL), brine (20 mL), dried (MgSO4), filtered and concentrated. The crude product was purified by flash chromatography using a Horizon purification system on a 25S column eluting with chloroform/acetone (2-20%) to afford tert-butyl methyl{(3R)-1-[1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl]pyrrolidin-3-yl}carbamate (104 mg, 91%)

Workup

  1. customquenched
  2. additionby adding water (1.0 mL)
  3. customThe tetrahydrofuran was removed in vacuo
  4. additionthe remaining aqueous solution was diluted with ethyl acetate (100 mL)
  5. washThe organic solution was washed with water (20 mL), brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by flash chromatography
  10. customa Horizon purification system on a 25S column
  11. washeluting with chloroform/acetone (2-20%)

Sources & evidence

ORD record
ord-308ae312147f4e3abfc2e7b0d1d8305c
Source dataset
uspto-grants-2010_06
Patent number
US07732604B2

Linked notes

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