Methylamine → HCID 90149279, compound

HRID 2202549Notes

Reaction equation

HRID 2202549 reaction equation
FC(F)(F)C([O-])=O.[CH2:8]([O:15][C:16]([NH:18][C@H:19]([C:28]1[NH:29][C:30]([I:33])=[CH:31][NH+:32]=1)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([OH:27])=O)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.CN.[CH3:36][N:37](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[I:33][C:30]1[NH:29][C:28]([C@@H:19]([NH:18][C:16](=[O:17])[O:15][CH2:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([NH:37][CH3:36])=[O:27])=[N:32][CH:31]=1

Participants

5

Reactant 3

HCID 6329Methylamine3×HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 90120308HCID 90120308, compound

Product 1

HCID 90149279HCID 90149279, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of D5 in DMF (0.3 M) was added methylamine (2.0 M solution in THF, 5.0 eq.) followed by HBTU (2.0 eq.). Solution pH was adjusted to basic value by addition of methylamine (2.0 M solution in THF, 2.5 eq.). Reaction mixture was stirred at room temperature for 1 h, then two more addition of HBTU (4.47 g, 28.5 mmol, 1.0 eq.) and methylamine (2.0 M solution in THF, 2.5 eq.) every 30 min were performed to reach completion of reaction. Solvent was concentrated under reduced pressure and the resulting residue was diluted with EtOAc, washed with sat. aq. NaHCO3, Brine, dried over Na2SO4 and concentrated under reduced pressure. The resulting crude was purified by column chromatography (eluent: petroleum ether/EtOAc from 4:1 to EtOAc) to give the title compound as a white solid. 1H-NMR (400 MHz, 300K, CDCl3) δ 12.11 (br s, 1H), 7.69-7.59 (m, 2H), 7.41-7.27 (m, 4H), 7.19 (s, 1H), 5.06 (d, 1H, J 12.8 Hz), 5.00 (d, 1H, J 12.8 Hz), 4.57 (m, 1H), 2.54 (d, 3H, J 4.8 Hz), 2.01 (t, 2H, J 7.4 Hz), 1.85-1.60 (m, 2H), 1.50-1.38 (m, 2H), 1.32-1.12 (m, 4H). MS (ES+) C19H25IN4O3: 485 (M+H)+.

Workup

  1. customReaction mixture
  2. customcompletion of reaction
  3. concentrationSolvent was concentrated under reduced pressure
  4. additionthe resulting residue was diluted with EtOAc
  5. washwashed with sat. aq. NaHCO3, Brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting crude was purified by column chromatography (eluent: petroleum ether/EtOAc from 4:1 to EtOAc)

Sources & evidence

ORD record
ord-cc5dbfbd427249f799d0ea6bfa6bc609
Source dataset
uspto-grants-2016_06
Patent number
US09365541B2

Reaction notes

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