Tetrahydrofuran → (3R,4R)-phenyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidine-1-carboxylate

HRID 1969777Notes

Reaction equation

HRID 1969777 reaction equation
Cl.[CH3:2][C@@H:3]1[CH2:8][CH2:7][NH:6][CH2:5][C@@H:4]1[C:9]1[N:13]2[C:14]3[CH:20]=[CH:19][NH:18][C:15]=3[N:16]=[CH:17][C:12]2=[CH:11][N:10]=1.C1COCC1.Cl[C:27]([O:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:28]>CC#N.CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:9]1([C@@H:4]2[C@H:3]([CH3:2])[CH2:8][CH2:7][N:6]([C:27]([O:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:28])[CH2:5]2)[N:13]2[C:14]3[CH:20]=[CH:19][NH:18][C:15]=3[N:16]=[CH:17][C:12]2=[CH:11][N:10]=1

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 15891Phenyl chloroformateHCID 672171491-((3R,4R)-4-methylpiperidin-3-yl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine hydrochloride

Product 1

HCID 58557404(3R,4R)-phenyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidine-1-carboxylateYield 12.9%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-((3R,4R)-4-methylpiperidin-3-yl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine hydrochloride (0.06 g, 0.21 mmol) in MeCN (1 mL) at about 0° C. was added TEA (0.06 mL, 0.41 mmol), THF (0.6 mL) and DMAP (0.006 g, 0.050 mmol) then phenyl chloroformate (0.026 mL, 0.206 mmol) and stirred for about 1 h. The reaction mixture was warmed to ambient temperature and concd under reduced pressure. The crude residue was dissolved in DCM (3 mL) and washed with water (2 mL), dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The crude residue was dissolved in DCM (5 mL) and washed with water (2 mL) and brine (2 mL), dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The material was purified by RP-HPLC (Table 1, Method g) to give (3R,4R)-phenyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidine-1-carboxylate (0.010 g, 11%): LC/MS (Table 1, Method b) Rt=1.95 min; MS m/z 376 (M+H)+.

Workup

  1. washwashed with water (2 mL)
  2. dry with materialdried over anhydrous MgSO4
  3. filtrationfiltered
  4. dissolutionThe crude residue was dissolved in DCM (5 mL)
  5. washwashed with water (2 mL) and brine (2 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. customThe material was purified by RP-HPLC (Table 1, Method g)

Sources & evidence

ORD record
ord-ba327ee5ac854fa19a5d4a21bf91e504
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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