Diisopropylethylamine → (3R,4R)-N-(2, 4-difluorophenyl)-3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidine-1-carboxamide

HRID 1969635Notes

Reaction equation

HRID 1969635 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.CCN(C(C)C)C(C)C.[F:30][C:31]1[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=1[N:38]=[C:39]=[O:40]>C(Cl)Cl>[F:30][C:31]1[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=1[NH:38][C:39]([N:6]1[CH2:7][CH2:8][C@@H:3]([CH3:2])[C@@H:4]([C:9]2[N:13]3[C:14]4[CH:20]=[CH:19][NH:18][C:15]=4[N:16]=[CH:17][C:12]3=[CH:11][N:10]=2)[CH2:5]1)=[O:40]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5932582,4-Difluorophenyl isocyanateHCID 672171491-((3R,4R)-4-methylpiperidin-3-yl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine hydrochloride

Product 1

HCID 67216495(3R,4R)-N-(2, 4-difluorophenyl)-3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidine-1-carboxamideYield 20.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

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 (0.05 g, 0.17 mmol, Example #5 Step J) and DIEA (0.03 mL, 0.17 mmol) in DCM (1.6 mL). The reaction mixture was stirred for about 5 min at ambient temperature then 2,4-difluoro-1-isocyanatobenzene (0.02 mL, 0.17 mmol) was added and the reaction mixture was stirred at ambient temperature for about 18 h. The reaction mixture was diluted with DCM (5 mL) and washed with water (2 mL). The aqueous layer was back extracted with DCM (2 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The material was purified by RP-HPLC (Table 1, Method e) to afford (3R,4R)-N-(2,4-difluorophenyl)-3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidine-1-carboxamide (0.014 g, 20%): LC/MS (Table 1, Method j) Rt=1.77 min; MS m/z 411 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for about 18 h
  2. washwashed with water (2 mL)
  3. extractionThe aqueous layer was back extracted with DCM (2 mL)
  4. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  5. filtrationfiltered
  6. customThe material was purified by RP-HPLC (Table 1, Method e)

Sources & evidence

ORD record
ord-0fa030a3c8f54b6281358d174d7e7a9f
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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