Potassium Carbonate → HCID 68051263, compound

HRID 2406223Notes

Reaction equation

HRID 2406223 reaction equation
N1(O[C:11]2[C:12]3[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:17][C:13]=3[N:14]=[CH:15][N:16]=2)C2C=CC=CC=2N=N1.[O:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][C@@H:35]([NH:44][C:45]2[CH:50]=[CH:49][C:48]([S:51]([NH2:54])(=[O:53])=[O:52])=[CH:47][C:46]=2[S:55]([C:58]([F:61])([F:60])[F:59])(=[O:57])=[O:56])[CH2:36][S:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH2:29][CH2:28]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O.CCOCC>[O:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][C@@H:35]([NH:44][C:45]2[CH:50]=[CH:49][C:48]([S:51]([NH:54][C:11]3[C:12]4[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:17][C:13]=4[N:14]=[CH:15][N:16]=3)(=[O:52])=[O:53])=[CH:47][C:46]=2[S:55]([C:58]([F:61])([F:59])[F:60])(=[O:57])=[O:56])[CH2:36][S:37][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:29][CH2:28]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 250584544-[[(1R)-3-(4-Morpholinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoromethyl)sulfonyl]benzenesulfonamideHCID 67054493HCID 67054493, compound

Product 1

HCID 68051263HCID 68051263, compoundYield 20.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent3×HCID 3283Diethyl EtherSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

tert-Butyl 4-(1H-benzo[d][1,2,3]triazol-1-yloxy)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (448 mg, 1.264 mmol), (R)-4-(4-morpholino-1-(phenylthio)butan-2-ylamino)-3(trifluoromethylsulfonyl)benzenesulfonamide (910 mg, 1.643 mmol), and potassium carbonate (524 mg, 3.79 mmol) were combined in N,N-dimethylformamide (6.3 mL) and stirred for 1.5 hours at 85° C. and then for 2.5 hours at 95° C. The reaction was then cooled to room temperature and stirred for 16 hours. The reaction was treated with water (˜30 mL) and sonicated. A dark brown solid stuck to the flask. The solid was washed several times with water and then several times with diethyl ether. This residue was then treated with methanol (˜15 mL), and the off-white precipitate formed was removed by filtration. The dark brown filtrate was concentrated in vacuo to afford a brown solid. The water and ether washes were combined and diluted with more water and ether. The layers were separated, and the organic layer was dried over sodium sulfate, filtered and concentrated down. This residue was combined with the brown solid and purified by flash chromatography on silica gel (0 to 10% methanol/ethyl acetate followed by 0 to 30% methanol/dichloromethane) to afford the title compound (199 mg, 13% yield). MS (ESI) m/e (M+H)+=773.5.

Workup

  1. waitfor 2.5 hours at 95° C
  2. temperatureThe reaction was then cooled to room temperature
  3. stirringstirred for 16 hours
  4. customsonicated
  5. washThe solid was washed several times with water
  6. additionThis residue was then treated with methanol (˜15 mL)
  7. customthe off-white precipitate formed
  8. customwas removed by filtration
  9. concentrationThe dark brown filtrate was concentrated in vacuo
  10. customto afford a brown solid
  11. customThe layers were separated
  12. dry with materialthe organic layer was dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated down
  15. custompurified by flash chromatography on silica gel (0 to 10% methanol/ethyl acetate followed by 0 to 30% methanol/dichloromethane)

Sources & evidence

ORD record
ord-fd922534fbcb4e2ca3682b72b492e613
Source dataset
uspto-grants-2014_08
Patent number
US08809352B2

Reaction notes

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