Methylamine → HCID 73055364, compound

HRID 1052247Notes

Reaction equation

HRID 1052247 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([O:32][CH3:33])[CH:31]=1)[CH2:6][CH2:7][C:8]1[N:9]=[C:10]2[CH:16]=[C:15]([C:17](O)=[O:18])[N:14](S(C3C=CC=CC=3)(=O)=O)[C:11]2=[N:12][CH:13]=1.CN.[CH3:36][N:37](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:6][CH2:7][C:8]2[N:9]=[C:10]3[CH:16]=[C:15]([C:17]([NH:37][CH3:36])=[O:18])[NH:14][C:11]3=[N:12][CH:13]=2)[CH:29]=[C:30]([O:32][CH3:33])[CH:31]=1

Participants

7

Reactant 5

HCID 6329MethylamineHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89963179HCID 89963179, compound

Product 1

HCID 73055364HCID 73055364, compoundYield 30.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 2-(3,5-dimethoxyphenethyl)-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine-6-carboxylic acid (27 mg, 57.8 μmol) in N,N-dimethylformamide (2 mL), methylamine (2.0 M in THF, 57.8 μL, 0.116 mmol), HATU (43.9 mg, 0.116 mmol) and N,N-diisopropylethylamine (40.2 μL, 0.231 mmol) were added sequentially at ambient temperature. After 1 hour, the reaction was quenched with saturated aq. NH4Cl, then extracted with methylene chloride. The combined organic layers were dried over MgSO4, and then concentrated. The residue was dissolved in methanol (2.0 mL), and potassium carbonate (16.0 mg, 0.116 mmol) was added. The reaction mixture was then warmed up to 60° C. After 1 hour, the crude mixture was allowed to warm to room temperature and was then purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at a flow rate of 30 mL/min) to give the desired product (6.0 mg, 30%) as its TFA salt. LCMS calculated for C18H21N4O3 (M+H)+: m/z=341.2. Found: 341.1.

Workup

  1. customthe reaction was quenched with saturated aq. NH4Cl
  2. extractionextracted with methylene chloride
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in methanol (2.0 mL)
  6. waitAfter 1 hour
  7. temperatureto warm to room temperature
  8. customwas then purified on RP-HPLC (XBridge C18 column
  9. washeluting with a gradient of acetonitrile/water containing 0.05% TFA, at a flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-61cd958e64454e4a99f722ead19006f2
Source dataset
uspto-grants-2016_07
Patent number
US09388185B2

Reaction notes

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