Cesium carbonate → (R)-1-(1-(4-fluorophenyl)ethyl)-3-(3-(methylamino)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea

HRID 590794Notes

Reaction equation

HRID 590794 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[C:8]([NH:30][CH3:31])=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1.[F:32][C:33]1[CH:38]=[CH:37][C:36]([C@H:39]([NH:41][C:42]([NH2:44])=[O:43])[CH3:40])=[CH:35][CH:34]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.O1CCOCC1>[F:32][C:33]1[CH:34]=[CH:35][C:36]([C@H:39]([NH:41][C:42]([NH:44][C:2]2[N:7]=[CH:6][C:5]3[C:8]([NH:30][CH3:31])=[N:9][N:10]([C:11]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)[C:4]=3[CH:3]=2)=[O:43])[CH3:40])=[CH:37][CH:38]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 117601722(R)-1-(1-(4-fluorophenyl)ethyl)urea2×HCID 1182724066-chloro-N-methyl-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-amine

Product 1

HCID 118272252(R)-1-(1-(4-fluorophenyl)ethyl)-3-(3-(methylamino)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea

Reagents, catalysts & solvents 2

HCID 25112535BrettphosCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

6-Chloro-N-methyl-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-amine (332 mg, 0.781 mmol), (R)-1-(1-(4-fluorophenyl)ethyl)urea (Intermediate 20C; 193 mg, 1.059 mmol), BrettPhos pre-catalyst (48.0 mg, 0.060 mmol), and cesium carbonate (759 mg, 2.330 mmol) were taken up in 1,4-dioxane (6 mL) in a 20 mL microwave vial. The vial was evacuated and back-filled with N2 (×3) and the reaction was stirred at 100° C. for 3 h. Room temperature was attained, the reaction mixture was filtered through Celite, eluting with MeOH, and the filtrate was concentrated in vacuo. Purification of the residue by flash chromatography (0-100% EtOAc-DCM) gave (R)-1-(1-(4-fluorophenyl)ethyl)-3-(3-(methylamino)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea. MS ESI calc'd. For C35H31FN6O [M+1]+ 571. found 571.

Workup

  1. customThe vial was evacuated
  2. additionback-filled with N2 (×3)
  3. customRoom temperature
  4. filtrationthe reaction mixture was filtered through Celite
  5. washeluting with MeOH
  6. concentrationthe filtrate was concentrated in vacuo
  7. customPurification of the residue by flash chromatography (0-100% EtOAc-DCM)

Sources & evidence

ORD record
ord-31a54a8e85754d888bcdca60f0dcc2db
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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