Methylamine → HCID 59540619, compound

HRID 1677502Notes

Reaction equation

HRID 1677502 reaction equation
CO[C:3]([C:5]1([CH3:31])[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]3[N:17]=[C:18]4[C:24]([C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:23][NH:22][C:19]4=[N:20][CH:21]=3)[CH:11]=2)[CH2:6]1)=[O:4].[OH-].[K+].C(C1NC=CN=1)([C:36]1[NH:37]C=CN=1)=O.CN>CN(C)C=O.CO>[CH3:36][NH:37][C:3]([C:5]1([CH3:31])[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]3[N:17]=[C:18]4[C:24]([C:25](=[O:30])[C:26]([CH3:27])([CH3:29])[CH3:28])=[CH:23][NH:22][C:19]4=[N:20][CH:21]=3)[CH:11]=2)[CH2:6]1)=[O:4]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 14797Potassium HydroxideHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 59540605HCID 59540605, compound

Product 1

HCID 59540619HCID 59540619, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

1-{3-[7-(2,2-Dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-phenyl}-3-methyl-pyrrolidine-3-carboxylic acid methylamide was prepared by treating 1-{3-[7-(2,2-dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-phenyl}-3-methyl-pyrrolidine-3-carboxylic acid methyl ester (190 mg, 0.3 mmol) with methanol (3 mL) and potassium hydroxide (2 mL, 0.5 M aqueous). Upon partitioning the mixture between 10% aqueous acetic acid and ethyl acetate, the desired acid (110 mg, 0.27 mmol) was dissolved in N,N-dimethylformamide (3 mL) and treated with carbonyl diimidazole (46 mg, 0.28 mmol) and heated to 65° C. for 2 hours. Methylamine (2 mL) was condensed at −20° C. in heavy-walled vessel. The mixture above was added and the vessel was immediately sealed and heated to 50° C. for 5 days. Upon cooling, the volatiles were removed in vacuo and the residue partitioned between 2% aqueous acetic acid and ethyl acetate. The combined organic layers were aged over anhydrous sodium sulfate. The title compound was obtained as a powder (26 mg) following silica gel chromatography (eluant: 40 to 100% ethyl acetate-hexanes): m.p. 252-254° C.; MS m/z 419 (M+H).

Workup

  1. customUpon partitioning the mixture between 10% aqueous acetic acid and ethyl acetate
  2. customcondensed at −20° C. in heavy-walled vessel
  3. additionThe mixture above was added
  4. customthe vessel was immediately sealed
  5. temperatureheated to 50° C. for 5 days
  6. temperatureUpon cooling
  7. customthe volatiles were removed in vacuo
  8. customthe residue partitioned between 2% aqueous acetic acid and ethyl acetate

Sources & evidence

ORD record
ord-17b69ec72e6d4cb89719f0c486dd81c4
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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