Diisopropylethylamine → HCID 70873586, compound

HRID 2208883Notes

Reaction equation

HRID 2208883 reaction equation
[CH2:1]([N:3]([CH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)[C:4]1[C:9]([CH3:10])=[C:8]([C:11]([OH:13])=O)[CH:7]=[CH:6][N:5]=1)[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:53][CH2:54][C:55]1[C:56](=[O:63])[NH:57][C:58]([CH3:62])=[CH:59][C:60]=1[CH3:61]>CN(C=O)C.O.C(Cl)Cl>[CH3:61][C:60]1[CH:59]=[C:58]([CH3:62])[NH:57][C:56](=[O:63])[C:55]=1[CH2:54][NH:53][C:11]([C:8]1[CH:7]=[CH:6][N:5]=[C:4]([N:3]([CH2:1][CH3:2])[CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:9]=1[CH3:10])=[O:13]

Participants

8

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 70874168HCID 70874168, compound

Product 1

HCID 70873586HCID 70873586, compoundYield 22%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A stirred solution of 2-[ethyl(oxan-4-yl)amino]-3-methylpyridine-4-carboxylic acid (20 mg, 0.08 mmol) in dry DMF (1.0 ml) at 0° C. under nitrogen, was treated with HATU (37 mg, 0.1 mmol) and DIPEA (26 μl, 0.15 mmol) dropwise. The resulting solution was stirred for 10 minutes and then treated with 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 15 mg, 0.09 mmol). The resulting suspension was stirred at 0° C. for 20 minutes and then stirred at room temperature for 18.5 hours. The reaction mixture was cooled to 0° C. and retreated with HATU (120 mg, 0.31 mmol) and DIPEA (84 μl, 0.48 mmol). After stirring for 10 minutes, 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 49 mg, 0.29 mmol) was added. The reaction mixture was stirred for 1 hour at 0° C. and was then lifted out of the ice bath stirred at room temperature for 48 hours. The reaction mixture was diluted with water (20 ml) and CH2Cl2 (20 ml). The layers were separated and the aqueous phase was extracted with CH2Cl2 (3×15 ml). The combined organic phases were washed with water (2×25 ml), brine (2×25 ml), dried (MgSO4), filtered and concentrated in-vacuo. The crude residue was purified by column chromatography (10 g SNAP cartridge, Isolera, 0-40% MeOH:CH2Cl2 and 0-25% MeOH (containing 10% NH4OH):CH2Cl2) to give 6.7 mg (22% Yield) of the title compound as an off white solid. LC-MS 100%, m/z=399.1; 1H NMR (250 MHz, DMSO) δ 11.49 (s, 1H), 8.32 (t, J=4.9 Hz, 1H), 8.14 (d, J=4.9 Hz, 1H), 6.84 (d, J=4.9 Hz, 1H), 5.86 (s, 1H), 4.26 (d, J=4.7 Hz, 2H), 3.84 (dd, J=10.3, 3.5 Hz, 2H), 3.21 (dt, J=13.6, 4.6 Hz, 5H), 2.19 (s, 3H), 2.15 (s, 3H), 2.11 (s, 3H), 1.62 (dt, J=21.1, 6.6 Hz, 4H), 0.80 (t, J=6.9 Hz, 3H).

Workup

  1. stirringThe resulting suspension was stirred at 0° C. for 20 minutes
  2. stirringstirred at room temperature for 18.5 hours
  3. stirringAfter stirring for 10 minutes
  4. stirringThe reaction mixture was stirred for 1 hour at 0° C.
  5. stirringstirred at room temperature for 48 hours
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted with CH2Cl2 (3×15 ml)
  8. washThe combined organic phases were washed with water (2×25 ml), brine (2×25 ml)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated in-vacuo
  12. customThe crude residue was purified by column chromatography (10 g SNAP cartridge, Isolera, 0-40% MeOH:CH2Cl2 and 0-25% MeOH (containing 10% NH4OH):CH2Cl2)

Sources & evidence

ORD record
ord-5d4c3573f7704ecfa8e9e29809cba241
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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