Water → HCID 67355776, compound

HRID 627446Notes

Reaction equation

HRID 627446 reaction equation
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([N:22]5[C:29](=[O:30])[CH2:28][C@@H:27]6[NH:31][C@@H:24]([CH2:25][CH2:26]6)[CH2:23]5)=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[CH:8]=[C:7]2[C:32]([N:34]([CH3:36])[CH3:35])=[O:33])[CH2:5][CH2:4][CH2:3][CH2:2]1.FC(F)(F)S(O[CH2:43][C:44]([F:47])([F:46])[F:45])(=O)=O.O>CN(C)C=O>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([N:22]5[C:29](=[O:30])[CH2:28][C@H:27]6[N:31]([CH2:43][C:44]([F:47])([F:46])[F:45])[C@H:24]([CH2:25][CH2:26]6)[CH2:23]5)=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[CH:8]=[C:7]2[C:32]([N:34]([CH3:36])[CH3:35])=[O:33])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 962WaterHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 53377611HCID 53377611, compound

Product 1

HCID 67355776HCID 67355776, compoundYield 64.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A sample of 7-Cyclopentyl-N,N-dimethyl-2-(5-((1S,6R)-4-oxo-3,9-diazabicyclo[4.2.1]nonan-3-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (60 mg, 0.123 mmol) was combined with 2,2,2-trifluoroethyl trifluoromethanesulfonate (0.035 ml, 0.246 mmol) in dimethylformamide (1 mL) and heated to (80° C.) overnight. The reaction was then poured into water and extracted with ethyl acetate. The aqueous was washed with ethyl acetate. The organics were combined, dried over sodium sulfate, filtered and concentrated which gave a crude material that was purified by silica gel column chromatography which gave 7-cyclopentyl-N,N-dimethyl-2-(5-((1R,6S)-4-oxo-9-(2,2,2-trifluoroethyl)-3,9-diazabicyclo[4.2.1]nonan-3-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (45 mg) in 64% yield. 1H NMR (400 MHz, CDCl3) δ ppm 8.74 (s, 1H), 8.51 (d, J=9.09 Hz, 1H), 8.22 (s, 1H), 8.15 (d, J=2.53 Hz, 1H), 7.52 (dd, J=8.84, 2.78 Hz, 1H), 6.46 (s, 1H), 4.80 (t, J=8.59 Hz, 1H), 4.23 (d, J=13.64 Hz, 1H), 3.47 (m, 3H), 3.16 (s, 6H), 3.06 (m, 3H), 2.83 (dd, J=15.66, 7.07 Hz, 1H), 2.57 (dd, J=12.13, 8.59 Hz, 2H), 2.04 (m, 6H), 1.70 (m, 4H). MS m/z 571.6 (M+H)

Workup

  1. extractionextracted with ethyl acetate
  2. washThe aqueous was washed with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated which
  6. customgave a crude material that
  7. customwas purified by silica gel column chromatography which

Sources & evidence

ORD record
ord-af6adccfe5024693b3f896bd45eb1958
Source dataset
uspto-grants-2016_04
Patent number
US09309252B2

Reaction notes

Loading…