Methylamine → HCID 71209135, compound

HRID 1473086Notes

Reaction equation

HRID 1473086 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[C:10]([NH:14][C:15]3[N:20]=[C:19]([CH2:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[CH2:29][C:30]([OH:32])=O)[C:18]([C:33]([F:36])([F:35])[F:34])=[CH:17][N:16]=3)[CH:11]=[CH:12][CH:13]=2)[CH2:4][CH2:3]1.[CH3:37][N:38](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CN>CN(C=O)C>[CH3:37][NH:38][C:30](=[O:32])[CH2:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[CH2:22][CH2:21][C:19]1[C:18]([C:33]([F:35])([F:36])[F:34])=[CH:17][N:16]=[C:15]([NH:14][C:10]2[CH:11]=[CH:12][CH:13]=[C:8]([N:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)[CH:9]=2)[N:20]=1

Participants

6

Reactant 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68282902HCID 68282902, compound

Product 1

HCID 71209135HCID 71209135, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(2-(2-(2-((3-(4-Methylpiperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid (I68) (75.0 mg, 169 μmol) was dissolved in DMF (1 mL) then HATU (129 mg, 339 μmol), DIPEA (57 μL, 339 μmol) and methylamine (8.0 M in ethanol; 200 μL) were added. The resulting mixture was stirred at room temperature overnight then the volatiles were evaporated under reduced pressure. The residue was diluted with ethyl acetate and washed with 10% NaHCO3, the layers were separated and the organic layer was dried (MgSO4) then evaporated under reduced pressure to give a cream solid. The cream solid was adsorbed onto silica and chromatographed on silica gel (0-10% MeOH/DCM) to give the title compound (I8) (9.0 mg, 10%) as a solid; 1H NMR (400 MHz, CD3CN) δ 8.56 (d, J=0.6 Hz, 1H), 8.36-8.28 (m, 1H), 7.39 (s, 1H), 7.20 (ddd, J=5.6, 4.4, 1.9 Hz, 6H), 6.71-6.65 (m, 1H), 6.33-6.23 (m, 1H), 3.56 (s, 2H), 3.22-3.15 (m, 4H), 3.10 (s, 2H), 3.07 (s, 2H), 2.60 (d, J=4.7 Hz, 3H), 2.49-2.43 (m, 4H). LCMS Method C: rt 4.86 min; m/z 513.3.

Workup

  1. customthe volatiles were evaporated under reduced pressure
  2. additionThe residue was diluted with ethyl acetate
  3. washwashed with 10% NaHCO3
  4. customthe layers were separated
  5. dry with materialthe organic layer was dried (MgSO4)
  6. customthen evaporated under reduced pressure
  7. customto give a cream solid
  8. customchromatographed on silica gel (0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-6996e830199f41dfb95a7a967fd85199
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

Loading…