1-Piperidinecarbonyl chloride → ((3R,4R)-3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidin-1-yl)(piperidin-1-yl)methanone

HRID 1969597Notes

Reaction equation

HRID 1969597 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.[N:21]1([C:27](Cl)=[O:28])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1>C1COCC1.C(Cl)Cl>[C:9]1([C@@H:4]2[C@H:3]([CH3:2])[CH2:8][CH2:7][N:6]([C:27]([N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]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

5

Reactant 2

HCID 2420851-Piperidinecarbonyl chlorideHCID 672171491-((3R,4R)-4-methylpiperidin-3-yl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine hydrochloride

Product 1

HCID 58557829((3R,4R)-3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidin-1-yl)(piperidin-1-yl)methanoneYield 37.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A round bottom flask was charged with 1-((3R,4R)-4-methylpiperidin-3-yl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine hydrochloride (0.050 g, 0.17 mmol, Example #5, Step J), TEA (0.10 mL, 0.69 mmol) in THF (1.6 mL). The reaction mixture was stirred for about 5 min at ambient temperature and then piperidine-1-carbonyl chloride (0.019 g, 0.13 mmol) was added. The reaction was heated at about 45° C. for about 18 h, cooled to ambient temperature, and concd under reduced pressure. The crude product was dissolved in DCM (5 mL) and washed with water (3 mL), dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The material was purified by RP-HPLC (Table 1, Method f) to give ((3R,4R)-3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidin-1-yl)(piperidin-1-yl)methanone (0.018 g, 8%): LC/MS (Table 1, Method b) Rt=1.80 min; MS m/z 367 (M+H)+.

Workup

  1. temperatureThe reaction was heated at about 45° C. for about 18 h
  2. temperaturecooled to ambient temperature
  3. washwashed with water (3 mL)
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. customThe material was purified by RP-HPLC (Table 1, Method f)

Sources & evidence

ORD record
ord-7ffb64d9451f43a58d2514f474361043
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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