Methylamine → HCID 59208400, compound

HRID 2243035Notes

Reaction equation

HRID 2243035 reaction equation
[CH2:1]([N:3](CC)CC)C.CN.[CH2:10]([C:12]1[N:13]=[C:14]([C:17]2[CH:22]=[C:21]([NH:23][C:24]([NH:26][CH2:27][CH3:28])=[O:25])[N:20]=[CH:19][C:18]=2[C:29]2[CH:30]=[N:31][CH:32]=[C:33]([C:35](O)=[O:36])[CH:34]=2)[S:15][CH:16]=1)[CH3:11].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CO.CN(C=O)C>[CH2:27]([NH:26][C:24]([NH:23][C:21]1[N:20]=[CH:19][C:18]([C:29]2[CH:30]=[N:31][CH:32]=[C:33]([C:35]([NH:3][CH3:1])=[O:36])[CH:34]=2)=[C:17]([C:14]2[S:15][CH:16]=[C:12]([CH2:10][CH3:11])[N:13]=2)[CH:22]=1)=[O:25])[CH3:28]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59208374HCID 59208374, compound

Product 1

HCID 59208400HCID 59208400, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Triethylamine (30.6 mg, 0.30 mmol) and methanamine (0.075 mL, 0.15 mmol), (2M soln in methanol) were added to a solution of 4′-(4-ethylthiazol-2-yl)-6′-(3-ethylureido)-3,3′-bipyridine-5-carboxylic acid (Example 99, 60 mg, 0.15 mmol) in DMF (1.5 mL). The solution was stirred for 10 minutes and then 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (57.4 mg, 0.15 mmol) was added. The resulting light yellow solution was stirred at room temperature for one hour. A small aliquat was withdrawn and analyzed by LCMS. Since the reaction was not complete, one more equivalent of methylamine solution and HATU were added. The analysis and addition of methylamine and HATU was repeated 3-4 times, however, the reaction did not go to completion. It was then diluted with water and extracted with ethylacetate 2-3 times. The extract was washed with water (3 times), brine and dried over magnesium sulfate, then concentrated to give the title compound as an off-white solid, which was triturated with acetonitrile and lyophilized to remove excess solvent (15 mg). MS (ES) MH+: 411 for C20H22N6O2S; NMR: 1.08 (t, 3H); 1.11 (t, 3H); 2.64 (q, 2H); 2.79 (d, 3H); 3.17-3.22 (m, 2H); 7.40 (s, 1H); 7.66 (s, 1H); 8.12 (d, 1H); 8.16 (s, 1H); 8.28 (s, 1H); 8.55 (s, 1H); 8.68 (s, 1H); 8.99 (d, 1H); 9.02 (s, 1H); 9.44 (s, 1H).

Workup

  1. stirringThe resulting light yellow solution was stirred at room temperature for one hour
  2. customA small aliquat was withdrawn
  3. additionone more equivalent of methylamine solution and HATU were added
  4. additionThe analysis and addition of methylamine and HATU
  5. additionIt was then diluted with water
  6. extractionextracted with ethylacetate 2-3 times
  7. washThe extract was washed with water (3 times), brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-85bed297faff460b90499e1b4f529288
Source dataset
uspto-grants-2010_03
Patent number
US07674801B2

Reaction notes

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