Methyl iodide → HCID 71280233, compound

HRID 246743Notes

Reaction equation

HRID 246743 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:12]2=[N:13][C:14]([C:17]3[CH:25]=[CH:24][CH:23]=[C:22]4[C:18]=3[CH:19]=[N:20][NH:21]4)=[CH:15][N:16]=[C:11]2[N:10]([C:26]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:45]C([O-])(C)C.[K+].IC>C1COCC1>[C:1]([NH:5][C:6]([C:8]1[C:12]2=[N:13][C:14]([C:17]3[CH:25]=[CH:24][CH:23]=[C:22]4[C:18]=3[CH:19]=[N:20][N:21]4[CH3:45])=[CH:15][N:16]=[C:11]2[N:10]([C:26]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 23665647Potassium tert-butoxideHCID 71279856HCID 71279856, compound

Product 1

HCID 71280233HCID 71280233, compoundYield 40.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-tert-butyl-2-(1H-indazol-4-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (375 mg, 0.65 mmol) in dry THF (20 mL) was added potassium 2-methylpropan-2-olate (109 mg, 0.975 mmol) at 0° C. After stirring for 30 minutes, iodomethane (138 mg, 0.975 mmol) was added at 0° C. Then it was warmed to room temperature and stirred for 1 hour. Reaction mixture was quenched by the addition of water (2 mL), extracted with ethyl acetate (100 mL), then organic phase washed with water (3×10 mL) and brine (2×10 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (silica gel, 200-300 mesh, eluting with EtOAc: petroleum ether=1:3) to afford N-tert-butyl-2-(1-methyl-1H-indazol-4-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (154 mg, 40%) as a white solid. LCMS: (M+H)+=591; 1H NMR (300 MHz, CDCl3): δ 8.54 (s, 1H), 8.50 (s, 1H), 8.40 (s, 1H), 8.35 (s, 1H), 7.53-7.47 (m, 3H), 7.32-7.27 (m, 9H), 7.24-7.19 (m, 6H), 4.14 (s, 3H), 1.52 (s, 9H).

Workup

  1. stirringstirred for 1 hour
  2. customReaction mixture
  3. customwas quenched by the addition of water (2 mL)
  4. extractionextracted with ethyl acetate (100 mL)
  5. washorganic phase washed with water (3×10 mL) and brine (2×10 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (silica gel, 200-300 mesh, eluting with EtOAc: petroleum ether=1:3)

Sources & evidence

ORD record
ord-9557ef6c867a47d8b5f7700cd4cd1050
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…