N-methyl-2-pyrrolidone → HCID 53330218, compound

HRID 517978Notes

Reaction equation

HRID 517978 reaction equation
[CH3:1][N:2]1[C:10]2[CH:9]=[C:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)=[C:13]([C:26]([F:29])([F:28])[F:27])[CH:12]=3)[N:7]=[C:6]([C:30]#[N:31])[C:5]=2[N:4]=[N:3]1.CCN(C(C)C)C(C)C.CN(C(ON1N=[N:56][C:51]2[CH:52]=[CH:53]C=N[C:50]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1C(=[O:71])CCC1>CCOC(C)=O>[NH2:56][C:51]1([C:50]([N:23]2[CH2:22][CH2:21][CH:20]([CH2:19][CH2:18][O:17][C:14]3[CH:15]=[CH:16][C:11]([C:8]4[N:7]=[C:6]([C:30]#[N:31])[C:5]5[N:4]=[N:3][N:2]([CH3:1])[C:10]=5[CH:9]=4)=[CH:12][C:13]=3[C:26]([F:29])([F:28])[F:27])[CH2:25][CH2:24]2)=[O:71])[CH2:53][CH2:52]1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67294093HCID 67294093, compound

Product 1

HCID 53330218HCID 53330218, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

1-Methyl-6-(4-(2-(piperidin-4-yl)ethoxy)-3-(trifluoromethyl)phenyl)-1H-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrile (76 mg), Boc-1-aminocyclopropane-1-carboxylic (71.1 mg) and DIPEA (146 μl) were dissolved in NMP (2 ml) and HATU (0.265 mmol, 101 mg) was then added. The reaction was stirred at room temperature for 72 hours then diluted with EtOAc (20 ml) and washed with 1:1 saturated sodium bicarbonate solution/water (3×15 ml). Organics were dried over sodium sulphate and solvent evaporated under reduced pressure. The resulting residue was re-dissolved in DCM (1 ml) and acetonitrile (200 μl) and trifluoroacetic acid (200 μl) added. The mixture was stirred for 30 minutes at room temperature then solvent evaporated under reduced pressure. Toluene (500 μl) was added and then removed under reduced pressure. The resulting brown residue was purified by flash chromatography (10 g silica column, DCM to 5% MeOH in DCM gradient). Solvent was evaporated under reduced pressure and the resulting solid was washed with DCM and ether and dried under vacuum to afford desired product 6-(4-(2-(1-(1-aminocyclopropanecarbonyl)piperidin-4-yl)ethoxy)-3-(trifluoromethyl)phenyl)-1-methyl-1H-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrile (52% yield) as a solid.

Workup

  1. washwashed with 1:1 saturated sodium bicarbonate solution/water (3×15 ml)
  2. dry with materialOrganics were dried over sodium sulphate and solvent
  3. customevaporated under reduced pressure
  4. dissolutionThe resulting residue was re-dissolved in DCM (1 ml)
  5. additionacetonitrile (200 μl) and trifluoroacetic acid (200 μl) added
  6. stirringThe mixture was stirred for 30 minutes at room temperature
  7. customsolvent evaporated under reduced pressure
  8. additionToluene (500 μl) was added
  9. customremoved under reduced pressure
  10. customThe resulting brown residue was purified by flash chromatography (10 g silica column, DCM to 5% MeOH in DCM gradient)
  11. customSolvent was evaporated under reduced pressure
  12. washthe resulting solid was washed with DCM and ether
  13. customdried under vacuum

Sources & evidence

ORD record
ord-8f296cbe5e8f4bb984283a0194296ed7
Source dataset
uspto-grants-2015_08
Patent number
US09115126B2

Reaction notes

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