Ammonia → 2-[4-(1-Aminocyclobutyl)phenyl]-3-phenylimidazo[1,2-a]pyrazine-6-carboxamide

HRID 1774947Notes

Reaction equation

HRID 1774947 reaction equation
C(OC([NH:8][C:9]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[N:20]=[C:21]4[CH:26]=[N:25][C:24]([C:27](OCC)=[O:28])=[CH:23][N:22]4[C:32]=3[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:15][CH:14]=2)[CH2:12][CH2:11][CH2:10]1)=O)(C)(C)C.[NH3:39]>>[NH2:8][C:9]1([C:13]2[CH:14]=[CH:15][C:16]([C:19]3[N:20]=[C:21]4[CH:26]=[N:25][C:24]([C:27]([NH2:39])=[O:28])=[CH:23][N:22]4[C:32]=3[C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)=[CH:17][CH:18]=2)[CH2:10][CH2:11][CH2:12]1

Participants

3

Reactant 2

HCID 222AmmoniaHCID 89691425Ethyl 2-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-3-phenylimidazo[1,2-a]pyrazine-6-carboxylate

Product 1

HCID 716571762-[4-(1-Aminocyclobutyl)phenyl]-3-phenylimidazo[1,2-a]pyrazine-6-carboxamide

Procedure

A solution of ethyl 2-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-3-phenylimidazo[1,2-a]pyrazine-6-carboxylate [Int-5] (70 mg, 0.14 mmol, 1.0 eq) in 2.0 mL ammonia (7M solution in methanol, ˜100 eq) was heated to 130° C. for 5 h in a single mode microwave oven. The volatile components were removed by the use of a rotary evaporator. The crude amide detected by UPLC was directly forwarded to the deprotection step. Therefore, the raw material was dissolved in 1.3 mL DCM/methanol (5/3) and 0.61 mL of 4 M hydrogenchloride in dioxane were added. The solution was stirred overnight at room temperature. The mixture was poured onto ice, made alkaline with aqueous sodium hydroxide (2 N) and extracted with DCM. The combined organic phases were washed with brine and dried with sodium sulphate. The solvent was using a rotary evaporator and the crude material was purified via MPLC (Biotage Isolera, 25 g Snap-cartridge; eluent: hexane/ethyl acetate (1/1)→ethyl acetate) to deliver 20 mg (40%) of the title compound.

Workup

  1. customThe volatile components were removed by the use of a rotary evaporator
  2. dissolutionTherefore, the raw material was dissolved in 1.3 mL DCM/methanol (5/3)
  3. addition0.61 mL of 4 M hydrogenchloride in dioxane were added
  4. additionThe mixture was poured onto ice
  5. extractionextracted with DCM
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried with sodium sulphate
  8. customa rotary evaporator
  9. customthe crude material was purified via MPLC (Biotage Isolera, 25 g Snap-cartridge; eluent: hexane/ethyl acetate (1/1)→ethyl acetate)

Sources & evidence

ORD record
ord-e26b51c6323c4b5386c85106630b7d1c
Source dataset
uspto-grants-2016_02
Patent number
US09260435B2

Reaction notes

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