Diisopropylethylamine → HCID 46221270, compound

HRID 1094780Notes

Reaction equation

HRID 1094780 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[C:5]([N:11]2[CH:15]=[CH:14][CH:13]=[N:12]2)=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[C@H:47]12[CH2:53][C@H:52]1[CH2:51][C@@H:50]([CH2:54][NH:55][C:56]1[CH:61]=[N:60][C:59]([C:62]([F:65])([F:64])[F:63])=[CH:58][N:57]=1)[NH:49][CH2:48]2.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:1][C:2]1[N:7]=[C:6]([C:8]([N:49]2[C@H:50]([CH2:54][NH:55][C:56]3[CH:61]=[N:60][C:59]([C:62]([F:65])([F:63])[F:64])=[CH:58][N:57]=3)[CH2:51][C@H:52]3[C@H:47]([CH2:53]3)[CH2:48]2)=[O:10])[C:5]([N:11]2[CH:15]=[CH:14][CH:13]=[N:12]2)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 593636726-Methyl-3-(1H-pyrazol-1-yl)picolinic acidHCID 59396007N-[(1S,4S,6S)-3-azabicyclo[4.1.0]hept-4-ylmethyl]-5-(trifluoromethyl)-2-pyrazinamine

Product 1

HCID 46221270HCID 46221270, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

6-methyl-3-(1H-pyrazol-1-yl)-2-pyridinecarboxylic acid D38 (24.63 mg) was dissolved in 1 ml of DMF, then TBTU (46.0 mg, 0.143 mmol) and DIPEA (0.025 ml, 0.143 mmol) were added. The suspension was stirred for 30 minutes at room temperature. N-[(1S,4S,6S)-3-azabicyclo[4.1.0]hept-4-ylmethyl]-5-(trifluoromethyl)-2-pyrazinamine D31 (30 mg) dissolved in 1 ml of DMF was added and the reaction was stirred overnight at room temperature. NaHCO3 saturated solution were added, and the aqueous layer was extracted with of DCM. The organic layers were collected together, dried through a phase separator and concentrated under vacuum to give a crude which was purified by SCX chromatography (column size 5 g). A second purification was performed by silica —NH chromatography (Biotage SP—column size 11 g, using Cy:EtOAc=5:5 to EtOAc). It was recovered the title compound E5 (22 mg). UPLC: (Acid Final_QC): rt=0.81 and 0.85 minutes (rotamers present), peaks observed: 458 (M+1). C22H22F3N7O requires 457. 1H NMR (400 MHz, CDCl3) δ ppm 8.29 (s, 1 H), 7.85-7.77 (m, 3 H), 7.52 (s, 1 H), 7.38-7.32 (m, 1 H), 7.05-6.89 (m, 1 H) 6.35-6.30 (m, 1 H) 4.58-4.37 (m, 1 H), 3.77-3.66 (m, 1 H), 3.65-3.37 (m, 2 H), 2.65 (s, 3 H), 2.50-2.36 (m, 2 H), 1.42-0.83 (m, 3 H), 0.82-0.71 (m, 1 H), 0.15-0.06 (m, 1 H).

Workup

  1. additionwas added
  2. stirringthe reaction was stirred overnight at room temperature
  3. extractionthe aqueous layer was extracted with of DCM
  4. customThe organic layers were collected together
  5. customdried through a phase separator
  6. concentrationconcentrated under vacuum
  7. customto give a crude which
  8. customwas purified by SCX chromatography (column size 5 g)
  9. customA second purification
  10. customIt was recovered the title compound E5 (22 mg)
  11. customrt=0.81 and 0.85 minutes (rotamers present)

Sources & evidence

ORD record
ord-be7efe91cd59420485d5dbc606883041
Source dataset
uspto-grants-2012_03
Patent number
US08133908B2

Reaction notes

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