Potassium Carbonate → HCID 178437162, compound

HRID 707315Notes

Reaction equation

HRID 707315 reaction equation
C(O[C:6](=O)[NH:7][C@H:8]1[CH2:11][C@H:10]([N:12]2[C:16]3=[N:17][CH:18]=[CH:19][CH:20]=[C:15]3[C:14]([CH3:22])([CH3:21])[C:13]2=[O:23])[CH2:9]1)(C)(C)C.ClC1[N:31]=[CH:30][C:29]([CH2:32][CH3:33])=[CH:28][N:27]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O>[CH2:32]([C:29]1[CH:28]=[N:27][C:6]([NH:7][C@H:8]2[CH2:9][C@H:10]([N:12]3[C:16]4=[N:17][CH:18]=[CH:19][CH:20]=[C:15]4[C:14]([CH3:21])([CH3:22])[C:13]3=[O:23])[CH2:11]2)=[N:31][CH:30]=1)[CH3:33]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 35727632-Chloro-5-ethylpyrimidineHCID 178454100HCID 178454100, compound2×

Product 1

HCID 178437162HCID 178437162, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

1-(Trans-3-aminocyclobutyl)-3,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-2(3H)-one hydrochloride (intermediate 26, 100 mg, 0.329 mmol), 2-chloro-5-ethylpyrimidine (0.047 mL, 0.329 mmol), and potassium carbonate (0.079 mL, 1.315 mmol) were mixed in DMSO (0.7 mL) in a microwave vial. The reaction mixture was stirred at 80° C. for 16 hours. The temperature was increased to 100° C. and the reaction stirred for another 9 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over magnesium sulfate, and concentrated. The resulting crude product was purified via silica gel flash column chromatography eluting with 0 to 100% ethyl acetate in hexanes to yield 1-(trans-3-((5-ethylpyrimidin-2-yl)amino)cyclobutyl)-3,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-2(3H)-one as an off-white solid. M+1: 338.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.14 (t, J=7.63 Hz, 3 H) 1.31 (s, 6 H) 2.26-2.37 (m, 2 H) 2.43 (q, J=7.63 Hz, 2 H) 3.15-3.26 (m, 2 H) 4.47-4.62 (m, 1 H) 5.16 (quin, J=8.20 Hz, 1 H) 7.07 (dd, J=7.24, 5.28 Hz, 1 H) 7.48 (d, J=6.46 Hz, 1 H) 7.75 (dd, J=7.24, 1.76 Hz, 1 H) 8.21 (dd, J=5.28, 1.56 Hz, 2 H)

Workup

  1. temperatureThe temperature was increased to 100° C.
  2. stirringthe reaction stirred for another 9 hours
  3. extractionextracted with ethyl acetate
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe resulting crude product was purified via silica gel flash column chromatography
  9. washeluting with 0 to 100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-b3afed1f4fa84cf1b4c713a67d8ec12a
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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