Cyclopentanecarbonyl chloride → N-((3-(5-(3-methyl-1-oxo-1-(2,2,2-trifluoroethylamino)butan-2-ylamino)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)methyl)cyclopentanecarboxamide

HRID 510218Notes

Reaction equation

HRID 510218 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]2[C:11]([C:12]3[CH:13]=[C:14]([NH:18][CH:19]([CH:28]([CH3:30])[CH3:29])[C:20]([NH:22][CH2:23][C:24]([F:27])([F:26])[F:25])=[O:21])[CH:15]=[N:16][CH:17]=3)=[CH:10][NH:9][C:6]2=[N:7][CH:8]=1.C(N(C(C)C)CC)(C)C.[CH:40]1([C:45](Cl)=[O:46])[CH2:44][CH2:43][CH2:42][CH2:41]1>CS(C)=O>[CH3:29][CH:28]([CH3:30])[CH:19]([NH:18][C:14]1[CH:13]=[C:12]([C:11]2[C:5]3[C:6](=[N:7][CH:8]=[C:3]([CH2:2][NH:1][C:45]([CH:40]4[CH2:44][CH2:43][CH2:42][CH2:41]4)=[O:46])[CH:4]=3)[NH:9][CH:10]=2)[CH:17]=[N:16][CH:15]=1)[C:20](=[O:21])[NH:22][CH2:23][C:24]([F:25])([F:26])[F:27]

Participants

5

Reactant 3

HCID 78284Cyclopentanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 894954382-(5-(5-(aminomethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamide

Product 1

HCID 89495559N-((3-(5-(3-methyl-1-oxo-1-(2,2,2-trifluoroethylamino)butan-2-ylamino)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)methyl)cyclopentanecarboxamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

2-(5-(5-(aminomethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamide 10-1c (30 mg, 0.071 mmol) was added to DMSO (0.5 ml) followed by the addition of diisopropylethylamine (0.031 ml, 0.178 mmol). Cyclopentanecarbonyl chloride (9.4 mg, 0.086 mmol) was added and the reaction stirred at room temperature for 3 hrs. The reaction was quenched by addition of methanol. The mixture was diluted with DMSO, filtered and purified by RP-HPLC (water:acetonitrile w/0.1% TFA, C-18, 15-50%). The pure fractions concentrated to remove acetonitrile and mixture neutralized with saturated sodium bicarbonate. The product was extracted with ethyl acetate (3×10 mL). The combined organics were then washed with brine, dried with sodium sulfate, filtered and concentrated to afford the product 10-1. LRMS (ESI) m/z 517.2 [(M+H)+; calcd for C26H31F3N6O2: 517.3

Workup

  1. customThe reaction was quenched by addition of methanol
  2. additionThe mixture was diluted with DMSO
  3. filtrationfiltered
  4. custompurified by RP-HPLC (water:acetonitrile w/0.1% TFA, C-18, 15-50%)
  5. concentrationThe pure fractions concentrated
  6. customto remove acetonitrile and mixture
  7. extractionThe product was extracted with ethyl acetate (3×10 mL)
  8. washThe combined organics were then washed with brine
  9. dry with materialdried with sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-a1dd87cd7285494bb38402bf7eb832f1
Source dataset
uspto-grants-2015_08
Patent number
US09096598B2

Reaction notes

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